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 5.729027 s

Results

genesymbol	prediction	probability	model	prediction problem	splicing	ClinVar	amino acid changes	variant type	dbSNP ID	protein length	file
GCH1	disease_causing	0.999426648806132	simple_aae		affected		R249S	single base exchange	rs104894442		show file
GCH1	disease_causing	0.999426648806132	simple_aae		affected		R249S	single base exchange	rs104894442		show file
GCH1	disease_causing	0.999999999999979	without_aae		affected			single base exchange	rs104894442		show file
GCH1	disease_causing	0.999999999999979	without_aae		affected			single base exchange	rs104894442		show file

Taster files

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999426648806132 (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM992168)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr14:55310741C>GN/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.747G>C
cDNA.936G>C
g.58830G>C

AA changes

R249S Score: 110 explain score(s)

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

249

frameshift

known variant

Reference ID: rs104894442
Allele 'G' was neither found in ExAC nor 1000G.
known disease mutation at this position, please check HGMD for details (HGMD ID CM992168)

known disease mutation at this position, please check HGMD for details (HGMD ID CM992168)
known disease mutation at this position, please check HGMD for details (HGMD ID CM992168)

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	1.638	1
	1.996	0.997
(flanking)	0.536	0.915

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 increased	58825	wt: 0.22 / mu: 0.26	wt: GGGAAGAGTTCCTGACTCTCATTAGGAGCTGAGCTTCATTC mu: GGGAAGAGTTCCTGACTCTCATTAGCAGCTGAGCTTCATTC	ctca\|TTAG
Donor marginally increased	58831	wt: 0.8385 / mu: 0.8938 (marginal change - not scored)	wt: TTAGGAGCTGAGCTT mu: TTAGCAGCTGAGCTT	AGGA\|gctg

distance from splice site

121

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

249

mutated

not conserved

249

Ptroglodytes

all identical

ENSPTRG00000006365

249

Mmulatta

all identical

ENSMMUG00000004084

249

Fcatus

all conserved

ENSFCAG00000008872

134

Mmusculus

all identical

ENSMUSG00000037580

240

Ggallus

all identical

ENSGALG00000012200

235

Trubripes

all identical

ENSTRUG00000015367

256

Drerio

all identical

ENSDARG00000070453

250

Dmelanogaster

not conserved

FBgn0003162

322

Celegans

no alignment

F32G8.6

n/a

Xtropicalis

all identical

ENSXETG00000012214

246

protein features

start (aa)	end (aa)	feature	details
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

747

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

936

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

58830

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

55310741

original gDNA sequence snippet

GAGTTCCTGACTCTCATTAGGAGCTGAGCTTCATTCAGTGT

altered gDNA sequence snippet

GAGTTCCTGACTCTCATTAGCAGCTGAGCTTCATTCAGTGT

original cDNA sequence snippet

GAGTTCCTGACTCTCATTAGGAGCTGAGCTTCATTCAGTGT

altered cDNA sequence snippet

GAGTTCCTGACTCTCATTAGCAGCTGAGCTTCATTCAGTGT

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

1.30 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: 0.999426648806132 (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM992168)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr14:55310741C>GN/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.747G>C
cDNA.908G>C
g.58830G>C

AA changes

R249S Score: 110 explain score(s)

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

249

frameshift

known variant

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	1.638	1
	1.996	0.997
(flanking)	0.536	0.915

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 increased	58825	wt: 0.22 / mu: 0.26	wt: GGGAAGAGTTCCTGACTCTCATTAGGAGCTGAGCTTCATTC mu: GGGAAGAGTTCCTGACTCTCATTAGCAGCTGAGCTTCATTC	ctca\|TTAG
Donor marginally increased	58831	wt: 0.8385 / mu: 0.8938 (marginal change - not scored)	wt: TTAGGAGCTGAGCTT mu: TTAGCAGCTGAGCTT	AGGA\|gctg

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

249

mutated

not conserved

249

Ptroglodytes

all identical

ENSPTRG00000006365

249

Mmulatta

all identical

ENSMMUG00000004084

249

Fcatus

all conserved

ENSFCAG00000008872

134

Mmusculus

all identical

ENSMUSG00000037580

240

Ggallus

all identical

ENSGALG00000012200

235

Trubripes

all identical

ENSTRUG00000015367

256

Drerio

all identical

ENSDARG00000070453

250

Dmelanogaster

not conserved

FBgn0003162

322

Celegans

no alignment

F32G8.6

n/a

Xtropicalis

all identical

ENSXETG00000012214

246

protein features

start (aa)	end (aa)	feature	details
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

747

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

908

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

58830

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

55310741

original gDNA sequence snippet

GAGTTCCTGACTCTCATTAGGAGCTGAGCTTCATTCAGTGT

altered gDNA sequence snippet

GAGTTCCTGACTCTCATTAGCAGCTGAGCTTCATTCAGTGT

original cDNA sequence snippet

GAGTTCCTGACTCTCATTAGGAGCTGAGCTTCATTCAGTGT

altered cDNA sequence snippet

GAGTTCCTGACTCTCATTAGCAGCTGAGCTTCATTCAGTGT

wildtype AA sequence

mutated AA sequence

speed

1.25 s

mutation t@sting

documentation

Prediction

disease causing

Model: without_aae, prob: 0.999999999999979 (explain)

Summary

known disease mutation at this position (HGMD CM992168)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr14:55310741C>GN/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.58830G>C

AA changes

N/A

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

N/A

frameshift

N/A

known variant

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	1.638	1
	1.996	0.997
(flanking)	0.536	0.915

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 increased	58825	wt: 0.22 / mu: 0.26	wt: GGGAAGAGTTCCTGACTCTCATTAGGAGCTGAGCTTCATTC mu: GGGAAGAGTTCCTGACTCTCATTAGCAGCTGAGCTTCATTC	ctca\|TTAG
Donor marginally increased	58831	wt: 0.8385 / mu: 0.8938 (marginal change - not scored)	wt: TTAGGAGCTGAGCTT mu: TTAGCAGCTGAGCTT	AGGA\|gctg

distance from splice site

154

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)

58830

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

55310741

original gDNA sequence snippet

GAGTTCCTGACTCTCATTAGGAGCTGAGCTTCATTCAGTGT

altered gDNA sequence snippet

GAGTTCCTGACTCTCATTAGCAGCTGAGCTTCATTCAGTGT

original cDNA sequence snippet

N/A

altered cDNA sequence snippet

N/A

wildtype AA sequence

mutated AA sequence

N/A

speed

1.11 s

mutation t@sting

documentation

Prediction

disease causing

Model: without_aae, prob: 0.999999999999979 (explain)

Summary

known disease mutation at this position (HGMD CM992168)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr14:55310741C>GN/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.58830G>C

AA changes

N/A

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

N/A

frameshift

N/A

known variant

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	1.638	1
	1.996	0.997
(flanking)	0.536	0.915

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 increased	58825	wt: 0.22 / mu: 0.26	wt: GGGAAGAGTTCCTGACTCTCATTAGGAGCTGAGCTTCATTC mu: GGGAAGAGTTCCTGACTCTCATTAGCAGCTGAGCTTCATTC	ctca\|TTAG
Donor marginally increased	58831	wt: 0.8385 / mu: 0.8938 (marginal change - not scored)	wt: TTAGGAGCTGAGCTT mu: TTAGCAGCTGAGCTT	AGGA\|gctg

distance from splice site

969

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)

58830

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

55310741

original gDNA sequence snippet

GAGTTCCTGACTCTCATTAGGAGCTGAGCTTCATTCAGTGT

altered gDNA sequence snippet

GAGTTCCTGACTCTCATTAGCAGCTGAGCTTCATTCAGTGT

original cDNA sequence snippet

N/A

altered cDNA sequence snippet

N/A

wildtype AA sequence

mutated AA sequence

N/A

speed

1.04 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