MutationTaster - study a chromosomal position

NEVER press reload or F5 - unless you want to start from the very beginning.
input seems to be ok - now mapping the variant to the different transcripts...
found 4 transcript(s)...
Querying Taster for transcript #1: ENST00000543643
Querying Taster for transcript #2: ENST00000491895
Querying Taster for transcript #3: ENST00000536224
Querying Taster for transcript #4: ENST00000395514
MT speed 3.99 s - this script 5.916408 s

Results

genesymbol	prediction	probability	model	prediction problem	splicing	ClinVar	amino acid changes	variant type	dbSNP ID	protein length	file
GCH1	disease_causing_automatic	0.999999999999332	simple_aae		affected	0	G108D	single base exchange	rs104894435		show file
GCH1	disease_causing_automatic	0.999999999999332	simple_aae		affected	0	G108D	single base exchange	rs104894435		show file
GCH1	disease_causing_automatic	0.999999999999332	simple_aae		affected	0	G108D	single base exchange	rs104894435		show file
GCH1	disease_causing_automatic	0.999999999999332	simple_aae		affected	0	G108D	single base exchange	rs104894435		show file

Taster files

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999999999999332 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM011347)
known disease mutation at this position (HGMD CM011348)
known disease mutation: rs9282 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr14:55369059C>TN/A show variant in all transcripts IGV

HGNC symbol

GCH1

Ensembl transcript ID

ENST00000543643

Genbank transcript ID

NM_001024070

UniProt peptide

P30793

alteration type

single base exchange

alteration region

CDS

DNA changes

c.323G>A
cDNA.467G>A
g.512G>A

AA changes

G108D Score: 94 explain score(s)

position(s) of altered AA
if AA alteration in CDS

108

frameshift

known variant

Reference ID: rs104894435
Allele 'T' was neither found in ExAC nor 1000G.
known disease mutation: rs9282 (pathogenic for Dystonia 5|Autosomal recessive DOPA responsive dystonia|GTP cyclohydrolase I deficiency) dbSNP NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM011347)

known disease mutation at this position, please check HGMD for details (HGMD ID CM011347)
known disease mutation at this position, please check HGMD for details (HGMD ID CM011348)

known disease mutation at this position, please check HGMD for details (HGMD ID CM011347)
known disease mutation at this position, please check HGMD for details (HGMD ID CM011348)
known disease mutation at this position, please check HGMD for details (HGMD ID CM011347)

known disease mutation at this position, please check HGMD for details (HGMD ID CM011347)
known disease mutation at this position, please check HGMD for details (HGMD ID CM011348)
known disease mutation at this position, please check HGMD for details (HGMD ID CM011347)
known disease mutation at this position, please check HGMD for details (HGMD ID CM011348)

regulatory features

Ap2alpha, Transcription Factor, Ap2alpha Transcription Factor Binding
Ap2gamma, Transcription Factor, Ap2gamma Transcription Factor Binding
DNase1, Open Chromatin, DNase1 Hypersensitive Site
E2F1, Transcription Factor, E2F1 Transcription Factor Binding
ELF1, Transcription Factor, ELF1 Transcription Factor Binding
Gabp, Transcription Factor, Gabp TF binding
H2AZ, Histone, Histone 2A variant Z
H2BK120ac, Histone, Histone 2B Lysine 120 Acetylation
H3K27ac, Histone, Histone 3 Lysine 27 Acetylation
H3K27me3, Histone, Histone 3 Lysine 27 Tri-Methylation
H3K4me2, Histone, Histone 3 Lysine 4 Di-Methylation
H3K4me3, Histone, Histone 3 Lysine 4 Tri-Methylation
H3K9ac, Histone, Histone 3 Lysine 9 Acetylation
H4K91ac, Histone, Histone 4 Lysine 91 Acetylation
Max, Transcription Factor, Max TF binding
PolII, Polymerase, RNA Polymerase II
Promoter Associated, Regulatory Feature, Promoter like regulatory feature
Sin3Ak20, Transcription Factor, Sin3Ak20 Transcription Factor Binding
TAF1, Transcription Factor, TAF1 Transcription Factor Binding
ZEB1, Transcription Factor, ZEB1 Transcription Factor Binding

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	1.223	1
	5.292	1
(flanking)	5.292	1

explain score(s) and/or inspect your position(s) in in UCSC Genome Browser

splice sites

effect	gDNA position	score	wt detection sequence	exon-intron border
Acc marginally increased	509	wt: 0.5046 / mu: 0.5430 (marginal change - not scored)	wt: GGCCATGCAGTTCTTCACCAAGGGCTACCAGGAGACCATCT mu: GGCCATGCAGTTCTTCACCAAGGACTACCAGGAGACCATCT	ccaa\|GGGC
Donor increased	516	wt: 0.70 / mu: 0.81	wt: GGCTACCAGGAGACC mu: GACTACCAGGAGACC	CTAC\|cagg

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

108

mutated

not conserved

108

Ptroglodytes

all identical

ENSPTRG00000006365

108

Mmulatta

all identical

ENSMMUG00000004084

108

Fcatus

no alignment

ENSFCAG00000008872

n/a

Mmusculus

all identical

ENSMUSG00000037580

Ggallus

all identical

ENSGALG00000012200

Trubripes

all identical

ENSTRUG00000015367

115

Drerio

all identical

ENSDARG00000070453

109

Dmelanogaster

all identical

FBgn0003162

181

Celegans

all identical

F32G8.6

Xtropicalis

all identical

ENSXETG00000012214

105

protein features

start (aa)	end (aa)	feature	details
108	110	HELIX		lost
113	115	TURN		might get lost (downstream of altered splice site)
130	141	STRAND		might get lost (downstream of altered splice site)
141	141	METAL	Zinc.	might get lost (downstream of altered splice site)
142	144	TURN		might get lost (downstream of altered splice site)
144	144	METAL	Zinc.	might get lost (downstream of altered splice site)
147	156	STRAND		might get lost (downstream of altered splice site)
165	176	HELIX		might get lost (downstream of altered splice site)
177	180	STRAND		might get lost (downstream of altered splice site)
182	197	HELIX		might get lost (downstream of altered splice site)
202	210	STRAND		might get lost (downstream of altered splice site)
206	206	CONFLICT	V -> I (in Ref. 9; CAA78908).	might get lost (downstream of altered splice site)
211	214	HELIX		might get lost (downstream of altered splice site)
212	212	METAL	Zinc.	might get lost (downstream of altered splice site)
215	217	TURN		might get lost (downstream of altered splice site)
224	230	STRAND		might get lost (downstream of altered splice site)
233	236	HELIX		might get lost (downstream of altered splice site)
238	248	HELIX		might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

702 / 702

position (AA) of stopcodon in wt / mu AA sequence

234 / 234

position of stopcodon in wt / mu cDNA

846 / 846

poly(A) signal

N/A

conservation
nucleotide level for all changes - no scoring up to now

N/A

position of start ATG in wt / mu cDNA

145 / 145

chromosome

strand

-1

last intron/exon boundary

859

theoretical NMD boundary in CDS

664

length of CDS

702

coding sequence (CDS) position

323

cDNA position
(for ins/del: last normal base / first normal base)

467

gDNA position
(for ins/del: last normal base / first normal base)

512

chromosomal position
(for ins/del: last normal base / first normal base)

55369059

original gDNA sequence snippet

CATGCAGTTCTTCACCAAGGGCTACCAGGAGACCATCTCAG

altered gDNA sequence snippet

CATGCAGTTCTTCACCAAGGACTACCAGGAGACCATCTCAG

original cDNA sequence snippet

CATGCAGTTCTTCACCAAGGGCTACCAGGAGACCATCTCAG

altered cDNA sequence snippet

CATGCAGTTCTTCACCAAGGACTACCAGGAGACCATCTCAG

wildtype AA sequence

MEKGPVRAPA EKPRGARCSN GFPERDPPRP GPSRPAEKPP RPEAKSAQPA DGWKGERPRS
EEDNELNLPN LAAAYSSILS SLGENPQRQG LLKTPWRAAS AMQFFTKGYQ ETISDVLNDA
IFDEDHDEMV IVKDIDMFSM CEHHLVPFVG KVHIGYLPNK QVLGLSKLAR IVEIYSRRLQ
VQERLTKQIA VAITEALRPA GVGVVVEATK SNKYNKGLSP LLSSCHLFVA ILK*

mutated AA sequence

MEKGPVRAPA EKPRGARCSN GFPERDPPRP GPSRPAEKPP RPEAKSAQPA DGWKGERPRS
EEDNELNLPN LAAAYSSILS SLGENPQRQG LLKTPWRAAS AMQFFTKDYQ ETISDVLNDA
IFDEDHDEMV IVKDIDMFSM CEHHLVPFVG KVHIGYLPNK QVLGLSKLAR IVEIYSRRLQ
VQERLTKQIA VAITEALRPA GVGVVVEATK SNKYNKGLSP LLSSCHLFVA ILK*

speed

1.13 s

All positions are in basepairs (bp) if not explicitly stated differently.
AA/aa: amino acid; CDS: coding sequence; mu: mutated; NMD: nonsense-mediated mRNA decay; nt: nucleotide; wt: wildtype; TGP: 1000 Genomes Project
back to results table

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999999999999332 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM011347)
known disease mutation at this position (HGMD CM011348)
known disease mutation: rs9282 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr14:55369059C>TN/A show variant in all transcripts IGV

HGNC symbol

GCH1

Ensembl transcript ID

ENST00000491895

Genbank transcript ID

NM_000161

UniProt peptide

P30793

alteration type

single base exchange

alteration region

CDS

DNA changes

c.323G>A
cDNA.512G>A
g.512G>A

AA changes

G108D Score: 94 explain score(s)

position(s) of altered AA
if AA alteration in CDS

108

frameshift

known variant

regulatory features

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	1.223	1
	5.292	1
(flanking)	5.292	1

explain score(s) and/or inspect your position(s) in in UCSC Genome Browser

splice sites

effect	gDNA position	score	wt detection sequence	exon-intron border
Acc marginally increased	509	wt: 0.5046 / mu: 0.5430 (marginal change - not scored)	wt: GGCCATGCAGTTCTTCACCAAGGGCTACCAGGAGACCATCT mu: GGCCATGCAGTTCTTCACCAAGGACTACCAGGAGACCATCT	ccaa\|GGGC
Donor increased	516	wt: 0.70 / mu: 0.81	wt: GGCTACCAGGAGACC mu: GACTACCAGGAGACC	CTAC\|cagg

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

108

mutated

not conserved

108

Ptroglodytes

all identical

ENSPTRG00000006365

108

Mmulatta

all identical

ENSMMUG00000004084

108

Fcatus

no alignment

ENSFCAG00000008872

n/a

Mmusculus

all identical

ENSMUSG00000037580

Ggallus

all identical

ENSGALG00000012200

Trubripes

all identical

ENSTRUG00000015367

115

Drerio

all identical

ENSDARG00000070453

109

Dmelanogaster

all identical

FBgn0003162

181

Celegans

all identical

F32G8.6

Xtropicalis

all identical

ENSXETG00000012214

105

protein features

start (aa)	end (aa)	feature	details
108	110	HELIX		lost
113	115	TURN		might get lost (downstream of altered splice site)
130	141	STRAND		might get lost (downstream of altered splice site)
141	141	METAL	Zinc.	might get lost (downstream of altered splice site)
142	144	TURN		might get lost (downstream of altered splice site)
144	144	METAL	Zinc.	might get lost (downstream of altered splice site)
147	156	STRAND		might get lost (downstream of altered splice site)
165	176	HELIX		might get lost (downstream of altered splice site)
177	180	STRAND		might get lost (downstream of altered splice site)
182	197	HELIX		might get lost (downstream of altered splice site)
202	210	STRAND		might get lost (downstream of altered splice site)
206	206	CONFLICT	V -> I (in Ref. 9; CAA78908).	might get lost (downstream of altered splice site)
211	214	HELIX		might get lost (downstream of altered splice site)
212	212	METAL	Zinc.	might get lost (downstream of altered splice site)
215	217	TURN		might get lost (downstream of altered splice site)
224	230	STRAND		might get lost (downstream of altered splice site)
233	236	HELIX		might get lost (downstream of altered splice site)
238	248	HELIX		might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

753 / 753

position (AA) of stopcodon in wt / mu AA sequence

251 / 251

position of stopcodon in wt / mu cDNA

942 / 942

poly(A) signal

N/A

conservation
nucleotide level for all changes - no scoring up to now

N/A

position of start ATG in wt / mu cDNA

190 / 190

chromosome

strand

-1

last intron/exon boundary

816

theoretical NMD boundary in CDS

576

length of CDS

753

coding sequence (CDS) position

323

cDNA position
(for ins/del: last normal base / first normal base)

512

gDNA position
(for ins/del: last normal base / first normal base)

512

chromosomal position
(for ins/del: last normal base / first normal base)

55369059

original gDNA sequence snippet

CATGCAGTTCTTCACCAAGGGCTACCAGGAGACCATCTCAG

altered gDNA sequence snippet

CATGCAGTTCTTCACCAAGGACTACCAGGAGACCATCTCAG

original cDNA sequence snippet

CATGCAGTTCTTCACCAAGGGCTACCAGGAGACCATCTCAG

altered cDNA sequence snippet

CATGCAGTTCTTCACCAAGGACTACCAGGAGACCATCTCAG

wildtype AA sequence

mutated AA sequence

speed

0.50 s

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999999999999332 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM011347)
known disease mutation at this position (HGMD CM011348)
known disease mutation: rs9282 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr14:55369059C>TN/A show variant in all transcripts IGV

HGNC symbol

GCH1

Ensembl transcript ID

ENST00000536224

Genbank transcript ID

NM_001024071

UniProt peptide

P30793

alteration type

single base exchange

alteration region

CDS

DNA changes

c.323G>A
cDNA.476G>A
g.512G>A

AA changes

G108D Score: 94 explain score(s)

position(s) of altered AA
if AA alteration in CDS

108

frameshift

known variant

regulatory features

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	1.223	1
	5.292	1
(flanking)	5.292	1

explain score(s) and/or inspect your position(s) in in UCSC Genome Browser

splice sites

effect	gDNA position	score	wt detection sequence	exon-intron border
Acc marginally increased	509	wt: 0.5046 / mu: 0.5430 (marginal change - not scored)	wt: GGCCATGCAGTTCTTCACCAAGGGCTACCAGGAGACCATCT mu: GGCCATGCAGTTCTTCACCAAGGACTACCAGGAGACCATCT	ccaa\|GGGC
Donor increased	516	wt: 0.70 / mu: 0.81	wt: GGCTACCAGGAGACC mu: GACTACCAGGAGACC	CTAC\|cagg

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

108

mutated

not conserved

108

Ptroglodytes

all identical

ENSPTRG00000006365

108

Mmulatta

all identical

ENSMMUG00000004084

108

Fcatus

no alignment

ENSFCAG00000008872

n/a

Mmusculus

all identical

ENSMUSG00000037580

Ggallus

all identical

ENSGALG00000012200

Trubripes

all identical

ENSTRUG00000015367

115

Drerio

all identical

ENSDARG00000070453

109

Dmelanogaster

all identical

FBgn0003162

181

Celegans

all identical

F32G8.6

Xtropicalis

all identical

ENSXETG00000012214

105

protein features

start (aa)	end (aa)	feature	details
108	110	HELIX		lost
113	115	TURN		might get lost (downstream of altered splice site)
130	141	STRAND		might get lost (downstream of altered splice site)
141	141	METAL	Zinc.	might get lost (downstream of altered splice site)
142	144	TURN		might get lost (downstream of altered splice site)
144	144	METAL	Zinc.	might get lost (downstream of altered splice site)
147	156	STRAND		might get lost (downstream of altered splice site)
165	176	HELIX		might get lost (downstream of altered splice site)
177	180	STRAND		might get lost (downstream of altered splice site)
182	197	HELIX		might get lost (downstream of altered splice site)
202	210	STRAND		might get lost (downstream of altered splice site)
206	206	CONFLICT	V -> I (in Ref. 9; CAA78908).	might get lost (downstream of altered splice site)
211	214	HELIX		might get lost (downstream of altered splice site)
212	212	METAL	Zinc.	might get lost (downstream of altered splice site)
215	217	TURN		might get lost (downstream of altered splice site)
224	230	STRAND		might get lost (downstream of altered splice site)
233	236	HELIX		might get lost (downstream of altered splice site)
238	248	HELIX		might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

642 / 642

position (AA) of stopcodon in wt / mu AA sequence

214 / 214

position of stopcodon in wt / mu cDNA

795 / 795

poly(A) signal

N/A

conservation
nucleotide level for all changes - no scoring up to now

N/A

position of start ATG in wt / mu cDNA

154 / 154

chromosome

strand

-1

last intron/exon boundary

780

theoretical NMD boundary in CDS

576

length of CDS

642

coding sequence (CDS) position

323

cDNA position
(for ins/del: last normal base / first normal base)

476

gDNA position
(for ins/del: last normal base / first normal base)

512

chromosomal position
(for ins/del: last normal base / first normal base)

55369059

original gDNA sequence snippet

CATGCAGTTCTTCACCAAGGGCTACCAGGAGACCATCTCAG

altered gDNA sequence snippet

CATGCAGTTCTTCACCAAGGACTACCAGGAGACCATCTCAG

original cDNA sequence snippet

CATGCAGTTCTTCACCAAGGGCTACCAGGAGACCATCTCAG

altered cDNA sequence snippet

CATGCAGTTCTTCACCAAGGACTACCAGGAGACCATCTCAG

wildtype AA sequence

mutated AA sequence

speed

1.22 s

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999999999999332 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM011347)
known disease mutation at this position (HGMD CM011348)
known disease mutation: rs9282 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr14:55369059C>TN/A show variant in all transcripts IGV

HGNC symbol

GCH1

Ensembl transcript ID

ENST00000395514

Genbank transcript ID

NM_001024024

UniProt peptide

P30793

alteration type

single base exchange

alteration region

CDS

DNA changes

c.323G>A
cDNA.484G>A
g.512G>A

AA changes

G108D Score: 94 explain score(s)

position(s) of altered AA
if AA alteration in CDS

108

frameshift

known variant

regulatory features

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	1.223	1
	5.292	1
(flanking)	5.292	1

explain score(s) and/or inspect your position(s) in in UCSC Genome Browser

splice sites

effect	gDNA position	score	wt detection sequence	exon-intron border
Acc marginally increased	509	wt: 0.5046 / mu: 0.5430 (marginal change - not scored)	wt: GGCCATGCAGTTCTTCACCAAGGGCTACCAGGAGACCATCT mu: GGCCATGCAGTTCTTCACCAAGGACTACCAGGAGACCATCT	ccaa\|GGGC
Donor increased	516	wt: 0.70 / mu: 0.81	wt: GGCTACCAGGAGACC mu: GACTACCAGGAGACC	CTAC\|cagg

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

108

mutated

not conserved

108

Ptroglodytes

all identical

ENSPTRG00000006365

108

Mmulatta

all identical

ENSMMUG00000004084

108

Fcatus

no alignment

ENSFCAG00000008872

n/a

Mmusculus

all identical

ENSMUSG00000037580

Ggallus

all identical

ENSGALG00000012200

Trubripes

all identical

ENSTRUG00000015367

115

Drerio

all identical

ENSDARG00000070453

109

Dmelanogaster

all identical

FBgn0003162

181

Celegans

all identical

F32G8.6

Xtropicalis

all identical

ENSXETG00000012214

105

protein features

start (aa)	end (aa)	feature	details
108	110	HELIX		lost
113	115	TURN		might get lost (downstream of altered splice site)
130	141	STRAND		might get lost (downstream of altered splice site)
141	141	METAL	Zinc.	might get lost (downstream of altered splice site)
142	144	TURN		might get lost (downstream of altered splice site)
144	144	METAL	Zinc.	might get lost (downstream of altered splice site)
147	156	STRAND		might get lost (downstream of altered splice site)
165	176	HELIX		might get lost (downstream of altered splice site)
177	180	STRAND		might get lost (downstream of altered splice site)
182	197	HELIX		might get lost (downstream of altered splice site)
202	210	STRAND		might get lost (downstream of altered splice site)
206	206	CONFLICT	V -> I (in Ref. 9; CAA78908).	might get lost (downstream of altered splice site)
211	214	HELIX		might get lost (downstream of altered splice site)
212	212	METAL	Zinc.	might get lost (downstream of altered splice site)
215	217	TURN		might get lost (downstream of altered splice site)
224	230	STRAND		might get lost (downstream of altered splice site)
233	236	HELIX		might get lost (downstream of altered splice site)
238	248	HELIX		might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

753 / 753

position (AA) of stopcodon in wt / mu AA sequence

251 / 251

position of stopcodon in wt / mu cDNA

914 / 914

poly(A) signal

N/A

conservation
nucleotide level for all changes - no scoring up to now

N/A

position of start ATG in wt / mu cDNA

162 / 162

chromosome

strand

-1

last intron/exon boundary

931

theoretical NMD boundary in CDS

719

length of CDS

753

coding sequence (CDS) position

323

cDNA position
(for ins/del: last normal base / first normal base)

484

gDNA position
(for ins/del: last normal base / first normal base)

512

chromosomal position
(for ins/del: last normal base / first normal base)

55369059

original gDNA sequence snippet

CATGCAGTTCTTCACCAAGGGCTACCAGGAGACCATCTCAG

altered gDNA sequence snippet

CATGCAGTTCTTCACCAAGGACTACCAGGAGACCATCTCAG

original cDNA sequence snippet

CATGCAGTTCTTCACCAAGGGCTACCAGGAGACCATCTCAG

altered cDNA sequence snippet

CATGCAGTTCTTCACCAAGGACTACCAGGAGACCATCTCAG

wildtype AA sequence

mutated AA sequence

speed

1.14 s

MutationTaster - study a chromosomal position

Results

Taster files

mutation t@sting

Prediction

disease causing

mutation t@sting

Prediction

disease causing

mutation t@sting

Prediction

disease causing

mutation t@sting

Prediction

disease causing

Problems