MutationTaster - study a chromosomal position

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input seems to be ok - now mapping the variant to the different transcripts...
found 2 transcript(s)...
Querying Taster for transcript #1: ENST00000382848
Querying Taster for transcript #2: ENST00000382844
MT speed 0 s - this script 4.522723 s

Results

genesymbol	prediction	probability	model	prediction problem	splicing	ClinVar	amino acid changes	variant type	dbSNP ID	protein length	file
GJB2	disease_causing_automatic	0.999999999534088	simple_aae			0	W77R	single base exchange	rs104894397		show file
GJB2	disease_causing_automatic	0.999999999534088	simple_aae			0	W77R	single base exchange	rs104894397		show file

Taster files

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999999999534088 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM970682)
known disease mutation: rs17003 (pathogenic)
protein features (might be) affected

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr13:20763492A>GN/A show variant in all transcripts IGV

HGNC symbol

GJB2

Ensembl transcript ID

ENST00000382848

Genbank transcript ID

NM_004004

UniProt peptide

P29033

alteration type

single base exchange

alteration region

CDS

DNA changes

c.229T>C
cDNA.367T>C
g.3546T>C

AA changes

W77R Score: 101 explain score(s)

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

frameshift

known variant

Reference ID: rs104894397

database	homozygous (G/G)	heterozygous	allele carriers
1000G	-	-	-
ExAC	0	1	1

known disease mutation: rs17003 (pathogenic for Deafness, autosomal recessive 1A|Deafness, autosomal dominant 3a|Deafness, autosomal recessive 1b|Nonsyndromic hearing loss and deafness|not provided|Rare genetic deafness) dbSNP NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM970682)

known disease mutation at this position, please check HGMD for details (HGMD ID CM970682)
known disease mutation at this position, please check HGMD for details (HGMD ID CM970682)

regulatory features

Promoter Associated, Regulatory Feature, Promoter like regulatory feature
Max, Transcription Factor, Max TF binding
Gabp, Transcription Factor, Gabp TF binding
H3K27me3, Histone, Histone 3 Lysine 27 Tri-Methylation
H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation
Gene Associated, Regulatory Feature, Gene associated regulatory feature
CTCF, Transcription Factor, CCCTC-binding factor
Gabp, Transcription Factor, Gabp TF binding (1)
DNase1, Open Chromatin, DNase1 Hypersensitive Site

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	6.087	1
	4.967	1
(flanking)	-0.969	0.522

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	3538	wt: 0.8764 / mu: 0.9216 (marginal change - not scored)	wt: CTACTTCCCCATCTCCCACATCCGGCTATGGGCCCTGCAGC mu: CTACTTCCCCATCTCCCACATCCGGCTACGGGCCCTGCAGC	acat\|CCGG
Acc marginally increased	3540	wt: 0.9595 / mu: 0.9692 (marginal change - not scored)	wt: ACTTCCCCATCTCCCACATCCGGCTATGGGCCCTGCAGCTG mu: ACTTCCCCATCTCCCACATCCGGCTACGGGCCCTGCAGCTG	atcc\|GGCT
Acc marginally increased	3541	wt: 0.8625 / mu: 0.9202 (marginal change - not scored)	wt: CTTCCCCATCTCCCACATCCGGCTATGGGCCCTGCAGCTGA mu: CTTCCCCATCTCCCACATCCGGCTACGGGCCCTGCAGCTGA	tccg\|GCTA
Donor marginally increased	3541	wt: 0.9896 / mu: 0.9939 (marginal change - not scored)	wt: CATCCGGCTATGGGC mu: CATCCGGCTACGGGC	TCCG\|gcta

distance from splice site

251

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

mutated

not conserved

Ptroglodytes

all identical

ENSPTRG00000031248

Mmulatta

all identical

ENSMMUG00000010522

Fcatus

all identical

ENSFCAG00000006961

Mmusculus

all identical

ENSMUSG00000046352

Ggallus

all identical

ENSGALG00000017136

Trubripes

no homologue

Drerio

all identical

ENSDARG00000042707

Dmelanogaster

no homologue

Celegans

no homologue

Xtropicalis

all identical

ENSXETG00000026112

protein features

start (aa)	end (aa)	feature	details
73	83	HELIX		lost
76	98	TRANSMEM	Helical; (Potential).	lost

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

681 / 681

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

227 / 227

position of stopcodon in wt / mu cDNA

819 / 819

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

139 / 139

chromosome

strand

-1

last intron/exon boundary

117

theoretical NMD boundary in CDS

cannot be calculated, too little distance between start ATG and last intron/exon boundary

length of CDS

681

coding sequence (CDS) position

229

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

367

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

3546

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

20763492

original gDNA sequence snippet

CCATCTCCCACATCCGGCTATGGGCCCTGCAGCTGATCTTC

altered gDNA sequence snippet

CCATCTCCCACATCCGGCTACGGGCCCTGCAGCTGATCTTC

original cDNA sequence snippet

CCATCTCCCACATCCGGCTATGGGCCCTGCAGCTGATCTTC

altered cDNA sequence snippet

CCATCTCCCACATCCGGCTACGGGCCCTGCAGCTGATCTTC

wildtype AA sequence

MDWGTLQTIL GGVNKHSTSI GKIWLTVLFI FRIMILVVAA KEVWGDEQAD FVCNTLQPGC
KNVCYDHYFP ISHIRLWALQ LIFVSTPALL VAMHVAYRRH EKKRKFIKGE IKSEFKDIEE
IKTQKVRIEG SLWWTYTSSI FFRVIFEAAF MYVFYVMYDG FSMQRLVKCN AWPCPNTVDC
FVSRPTEKTV FTVFMIAVSG ICILLNVTEL CYLLIRYCSG KSKKPV*

mutated AA sequence

MDWGTLQTIL GGVNKHSTSI GKIWLTVLFI FRIMILVVAA KEVWGDEQAD FVCNTLQPGC
KNVCYDHYFP ISHIRLRALQ LIFVSTPALL VAMHVAYRRH EKKRKFIKGE IKSEFKDIEE
IKTQKVRIEG SLWWTYTSSI FFRVIFEAAF MYVFYVMYDG FSMQRLVKCN AWPCPNTVDC
FVSRPTEKTV FTVFMIAVSG ICILLNVTEL CYLLIRYCSG KSKKPV*

speed

1.25 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: 0.999999999534088 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM970682)
known disease mutation: rs17003 (pathogenic)
protein features (might be) affected

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr13:20763492A>GN/A show variant in all transcripts IGV

HGNC symbol

GJB2

Ensembl transcript ID

ENST00000382844

Genbank transcript ID

N/A

UniProt peptide

P29033

alteration type

single base exchange

alteration region

CDS

DNA changes

c.229T>C
cDNA.428T>C
g.3546T>C

AA changes

W77R Score: 101 explain score(s)

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

frameshift

known variant

Reference ID: rs104894397

database	homozygous (G/G)	heterozygous	allele carriers
1000G	-	-	-
ExAC	0	1	1

regulatory features

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	6.087	1
	4.967	1
(flanking)	-0.969	0.522

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	3538	wt: 0.8764 / mu: 0.9216 (marginal change - not scored)	wt: CTACTTCCCCATCTCCCACATCCGGCTATGGGCCCTGCAGC mu: CTACTTCCCCATCTCCCACATCCGGCTACGGGCCCTGCAGC	acat\|CCGG
Acc marginally increased	3540	wt: 0.9595 / mu: 0.9692 (marginal change - not scored)	wt: ACTTCCCCATCTCCCACATCCGGCTATGGGCCCTGCAGCTG mu: ACTTCCCCATCTCCCACATCCGGCTACGGGCCCTGCAGCTG	atcc\|GGCT
Acc marginally increased	3541	wt: 0.8625 / mu: 0.9202 (marginal change - not scored)	wt: CTTCCCCATCTCCCACATCCGGCTATGGGCCCTGCAGCTGA mu: CTTCCCCATCTCCCACATCCGGCTACGGGCCCTGCAGCTGA	tccg\|GCTA
Donor marginally increased	3541	wt: 0.9896 / mu: 0.9939 (marginal change - not scored)	wt: CATCCGGCTATGGGC mu: CATCCGGCTACGGGC	TCCG\|gcta

distance from splice site

428

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

mutated

not conserved

Ptroglodytes

all identical

ENSPTRG00000031248

Mmulatta

all identical

ENSMMUG00000010522

Fcatus

all identical

ENSFCAG00000006961

Mmusculus

all identical

ENSMUSG00000046352

Ggallus

all identical

ENSGALG00000017136

Trubripes

no homologue

Drerio

all identical

ENSDARG00000042707

Dmelanogaster

no homologue

Celegans

no homologue

Xtropicalis

all identical

ENSXETG00000026112

protein features

start (aa)	end (aa)	feature	details
73	83	HELIX		lost
76	98	TRANSMEM	Helical; (Potential).	lost

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

681 / 681

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

227 / 227

position of stopcodon in wt / mu cDNA

880 / 880

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

200 / 200

chromosome

strand

-1

last intron/exon boundary

theoretical NMD boundary in CDS

cannot be calculated, too little distance between start ATG and last intron/exon boundary

length of CDS

681

coding sequence (CDS) position

229

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

428

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

3546

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

20763492

original gDNA sequence snippet

CCATCTCCCACATCCGGCTATGGGCCCTGCAGCTGATCTTC

altered gDNA sequence snippet

CCATCTCCCACATCCGGCTACGGGCCCTGCAGCTGATCTTC

original cDNA sequence snippet

CCATCTCCCACATCCGGCTATGGGCCCTGCAGCTGATCTTC

altered cDNA sequence snippet

CCATCTCCCACATCCGGCTACGGGCCCTGCAGCTGATCTTC

wildtype AA sequence

mutated AA sequence

speed

1.33 s

MutationTaster - study a chromosomal position

Results

Taster files

mutation t@sting

Prediction

disease causing

mutation t@sting

Prediction

disease causing

Problems