MutationTaster - study a chromosomal position

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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 0 s - this script 4.229387 s

Results

genesymbol	prediction	probability	model	prediction problem	splicing	ClinVar	amino acid changes	variant type	dbSNP ID	protein length	file
GCH1	disease_causing_automatic	0.999998875398612	simple_aae		affected	0	K224R	single base exchange	rs41298442		show file
GCH1	disease_causing_automatic	0.999998875398612	simple_aae		affected	0	K224R	single base exchange	rs41298442		show file
GCH1	disease_causing_automatic	0.99999999999999	without_aae		affected	0		single base exchange	rs41298442		show file
GCH1	disease_causing_automatic	0.99999999999999	without_aae		affected	0		single base exchange	rs41298442		show file

Taster files

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999998875398612 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
heterozygous in TGP or ExAC
known disease mutation at this position (HGMD CM960729)
known disease mutation: rs9283 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr14:55310817T>CN/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.671A>G
cDNA.860A>G
g.58754A>G

AA changes

K224R Score: 26 explain score(s)

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

224

frameshift

known variant

Reference ID: rs41298442

database	homozygous (C/C)	heterozygous	allele carriers
1000G	0	2	2
ExAC	0	44	44

known disease mutation: rs9283 (pathogenic for Dystonia 5|Autosomal recessive DOPA responsive dystonia|GTP cyclohydrolase I deficiency|not provided) dbSNP NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM960729)

known disease mutation at this position, please check HGMD for details (HGMD ID CM960729)
known disease mutation at this position, please check HGMD for details (HGMD ID CM960729)

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	0.358	0.999
	1.304	1
(flanking)	3.383	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
Donor marginally increased	58745	wt: 0.9216 / mu: 0.9238 (marginal change - not scored)	wt: GAAAATGAACAGCAA mu: GAAAATGAACAGCAG	AAAT\|gaac
Donor gained	58753	0.38	mu: ACAGCAGAACTGTGA	AGCA\|gaac

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

224

mutated

all conserved

224

Ptroglodytes

all identical

ENSPTRG00000006365

224

Mmulatta

all identical

ENSMMUG00000004084

224

Fcatus

all identical

ENSFCAG00000008872

109

Mmusculus

all identical

ENSMUSG00000037580

215

Ggallus

all identical

ENSGALG00000012200

210

Trubripes

all identical

ENSTRUG00000015367

231

Drerio

all identical

ENSDARG00000070453

225

Dmelanogaster

all identical

FBgn0003162

297

Celegans

not conserved

F32G8.6

196

Xtropicalis

all identical

ENSXETG00000012214

221

protein features

start (aa)	end (aa)	feature	details
224	230	STRAND		lost
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

671

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

860

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

58754

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

55310817

original gDNA sequence snippet

TGTACAGAAAATGAACAGCAAAACTGTGACCAGCACAATGT

altered gDNA sequence snippet

TGTACAGAAAATGAACAGCAGAACTGTGACCAGCACAATGT

original cDNA sequence snippet

TGTACAGAAAATGAACAGCAAAACTGTGACCAGCACAATGT

altered cDNA sequence snippet

TGTACAGAAAATGAACAGCAGAACTGTGACCAGCACAATGT

wildtype AA sequence

MEKGPVRAPA EKPRGARCSN GFPERDPPRP GPSRPAEKPP RPEAKSAQPA DGWKGERPRS
EEDNELNLPN LAAAYSSILS SLGENPQRQG LLKTPWRAAS AMQFFTKGYQ ETISDVLNDA
IFDEDHDEMV IVKDIDMFSM CEHHLVPFVG KVHIGYLPNK QVLGLSKLAR IVEIYSRRLQ
VQERLTKQIA VAITEALRPA GVGVVVEATH MCMVMRGVQK MNSKTVTSTM LGVFREDPKT
REEFLTLIRS *

mutated AA sequence

speed

0.21 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: 0.999998875398612 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
heterozygous in TGP or ExAC
known disease mutation at this position (HGMD CM960729)
known disease mutation: rs9283 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr14:55310817T>CN/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.671A>G
cDNA.832A>G
g.58754A>G

AA changes

K224R Score: 26 explain score(s)

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

224

frameshift

known variant

Reference ID: rs41298442

database	homozygous (C/C)	heterozygous	allele carriers
1000G	0	2	2
ExAC	0	44	44

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	0.358	0.999
	1.304	1
(flanking)	3.383	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
Donor marginally increased	58745	wt: 0.9216 / mu: 0.9238 (marginal change - not scored)	wt: GAAAATGAACAGCAA mu: GAAAATGAACAGCAG	AAAT\|gaac
Donor gained	58753	0.38	mu: ACAGCAGAACTGTGA	AGCA\|gaac

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

224

mutated

all conserved

224

Ptroglodytes

all identical

ENSPTRG00000006365

224

Mmulatta

all identical

ENSMMUG00000004084

224

Fcatus

all identical

ENSFCAG00000008872

109

Mmusculus

all identical

ENSMUSG00000037580

215

Ggallus

all identical

ENSGALG00000012200

210

Trubripes

all identical

ENSTRUG00000015367

231

Drerio

all identical

ENSDARG00000070453

225

Dmelanogaster

all identical

FBgn0003162

297

Celegans

not conserved

F32G8.6

196

Xtropicalis

all identical

ENSXETG00000012214

221

protein features

start (aa)	end (aa)	feature	details
224	230	STRAND		lost
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

671

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

832

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

58754

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

55310817

original gDNA sequence snippet

TGTACAGAAAATGAACAGCAAAACTGTGACCAGCACAATGT

altered gDNA sequence snippet

TGTACAGAAAATGAACAGCAGAACTGTGACCAGCACAATGT

original cDNA sequence snippet

TGTACAGAAAATGAACAGCAAAACTGTGACCAGCACAATGT

altered cDNA sequence snippet

TGTACAGAAAATGAACAGCAGAACTGTGACCAGCACAATGT

wildtype AA sequence

mutated AA sequence

speed

1.16 s

mutation t@sting

documentation

Prediction

disease causing

Model: without_aae, prob: 0.99999999999999 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

heterozygous in TGP or ExAC
known disease mutation at this position (HGMD CM960729)
known disease mutation: rs9283 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr14:55310817T>CN/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

intron

DNA changes

g.58754A>G

AA changes

N/A

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

N/A

frameshift

N/A

known variant

Reference ID: rs41298442

database	homozygous (C/C)	heterozygous	allele carriers
1000G	0	2	2
ExAC	0	44	44

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	0.358	0.999
	1.304	1
(flanking)	3.383	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
Donor marginally increased	58745	wt: 0.9216 / mu: 0.9238 (marginal change - not scored)	wt: GAAAATGAACAGCAA mu: GAAAATGAACAGCAG	AAAT\|gaac
Donor gained	58753	0.38	mu: ACAGCAGAACTGTGA	AGCA\|gaac

distance from splice site

230

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

N/A

protein features

start (aa)	end (aa)	feature	details
202	210	STRAND		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

N/A

AA sequence altered

N/A

position of stopcodon in wt / mu CDS

N/A

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

N/A

position of stopcodon in wt / mu cDNA

N/A

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

N/A

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

N/A

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

58754

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

55310817

original gDNA sequence snippet

TGTACAGAAAATGAACAGCAAAACTGTGACCAGCACAATGT

altered gDNA sequence snippet

TGTACAGAAAATGAACAGCAGAACTGTGACCAGCACAATGT

original cDNA sequence snippet

N/A

altered cDNA sequence snippet

N/A

wildtype AA sequence

mutated AA sequence

N/A

speed

0.91 s

mutation t@sting

documentation

Prediction

disease causing

Model: without_aae, prob: 0.99999999999999 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

heterozygous in TGP or ExAC
known disease mutation at this position (HGMD CM960729)
known disease mutation: rs9283 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr14:55310817T>CN/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

intron

DNA changes

g.58754A>G

AA changes

N/A

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

N/A

frameshift

N/A

known variant

Reference ID: rs41298442

database	homozygous (C/C)	heterozygous	allele carriers
1000G	0	2	2
ExAC	0	44	44

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	0.358	0.999
	1.304	1
(flanking)	3.383	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
Donor marginally increased	58745	wt: 0.9216 / mu: 0.9238 (marginal change - not scored)	wt: GAAAATGAACAGCAA mu: GAAAATGAACAGCAG	AAAT\|gaac
Donor gained	58753	0.38	mu: ACAGCAGAACTGTGA	AGCA\|gaac

distance from splice site

1045

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

N/A

protein features

start (aa)	end (aa)	feature	details
202	210	STRAND		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

N/A

AA sequence altered

N/A

position of stopcodon in wt / mu CDS

N/A

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

N/A

position of stopcodon in wt / mu cDNA

N/A

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

N/A

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

N/A

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

58754

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

55310817

original gDNA sequence snippet

TGTACAGAAAATGAACAGCAAAACTGTGACCAGCACAATGT

altered gDNA sequence snippet

TGTACAGAAAATGAACAGCAGAACTGTGACCAGCACAATGT

original cDNA sequence snippet

N/A

altered cDNA sequence snippet

N/A

wildtype AA sequence

mutated AA sequence

N/A

speed

0.12 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