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: ENST00000373366
Querying Taster for transcript #2: ENST00000373362
MT speed 0 s - this script 2.910386 s

Results

genesymbol	prediction	probability	model	prediction problem	splicing	ClinVar	amino acid changes	variant type	dbSNP ID	protein length	file
GJB3	disease_causing_automatic	7.42134676579017e-08	simple_aae		affected	0	N166S	single base exchange	rs121908851		show file
GJB3	disease_causing_automatic	7.42134676579017e-08	simple_aae		affected	0	N166S	single base exchange	rs121908851		show file

Taster files

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 7.42134676579017e-08 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM090826)
known disease mutation: rs6492 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr1:35250860A>GN/A show variant in all transcripts IGV

HGNC symbol

GJB3

Ensembl transcript ID

ENST00000373366

Genbank transcript ID

NM_024009

UniProt peptide

O75712

alteration type

single base exchange

alteration region

CDS

DNA changes

c.497A>G
cDNA.1112A>G
g.4071A>G

AA changes

N166S Score: 46 explain score(s)

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

166

frameshift

known variant

Reference ID: rs121908851

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

known disease mutation: rs6492 (pathogenic for Deafness, digenic, GJB2/GJB3) dbSNP NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM090826)

known disease mutation at this position, please check HGMD for details (HGMD ID CM090826)
known disease mutation at this position, please check HGMD for details (HGMD ID CM090826)

regulatory features

DNase1, Open Chromatin, DNase1 Hypersensitive Site
Gene Associated, Regulatory Feature, Gene associated regulatory feature
H3K27me3, Histone, Histone 3 Lysine 27 Tri-Methylation
H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation
Promoter Associated, Regulatory Feature, Promoter like regulatory feature

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	0.169	0.076
	0.012	0.086
(flanking)	0.829	0.285

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 gained	4070	0.79	mu: GTGCCAGCGTGGCCC	GCCA\|gcgt

distance from splice site

522

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

166

mutated

all conserved

166

Ptroglodytes

no homologue

Mmulatta

all identical

ENSMMUG00000022677

166

Fcatus

all identical

ENSFCAG00000014055

166

Mmusculus

all conserved

ENSMUSG00000042367

166

Ggallus

no homologue

Trubripes

no homologue

Drerio

all conserved

ENSDARG00000042866

159

Dmelanogaster

no homologue

Celegans

no homologue

Xtropicalis

all identical

ENSXETG00000016481

166

protein features

start (aa)	end (aa)	feature	details
150	187	TOPO_DOM	Extracellular (Potential).	lost
188	210	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
211	270	TOPO_DOM	Cytoplasmic (Potential).	might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

813 / 813

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

271 / 271

position of stopcodon in wt / mu cDNA

1428 / 1428

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

616 / 616

chromosome

strand

last intron/exon boundary

591

theoretical NMD boundary in CDS

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

length of CDS

813

coding sequence (CDS) position

497

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

1112

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

4071

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

35250860

original gDNA sequence snippet

GCGCCTGGTGCAGTGTGCCAACGTGGCCCCCTGCCCCAACA

altered gDNA sequence snippet

GCGCCTGGTGCAGTGTGCCAGCGTGGCCCCCTGCCCCAACA

original cDNA sequence snippet

GCGCCTGGTGCAGTGTGCCAACGTGGCCCCCTGCCCCAACA

altered cDNA sequence snippet

GCGCCTGGTGCAGTGTGCCAGCGTGGCCCCCTGCCCCAACA

wildtype AA sequence

MDWKTLQALL SGVNKYSTAF GRIWLSVVFV FRVLVYVVAA ERVWGDEQKD FDCNTKQPGC
TNVCYDNYFP ISNIRLWALQ LIFVTCPSLL VILHVAYREE RERRHRQKHG DQCAKLYDNA
GKKHGGLWWT YLFSLIFKLI IEFLFLYLLH TLWHGFNMPR LVQCANVAPC PNIVDCYIAR
PTEKKIFTYF MVGASAVCIV LTICELCYLI CHRVLRGLHK DKPRGGCSPS SSASRASTCR
CHHKLVEAGE VDPDPGNNKL QASAPNLTPI *

mutated AA sequence

MDWKTLQALL SGVNKYSTAF GRIWLSVVFV FRVLVYVVAA ERVWGDEQKD FDCNTKQPGC
TNVCYDNYFP ISNIRLWALQ LIFVTCPSLL VILHVAYREE RERRHRQKHG DQCAKLYDNA
GKKHGGLWWT YLFSLIFKLI IEFLFLYLLH TLWHGFNMPR LVQCASVAPC PNIVDCYIAR
PTEKKIFTYF MVGASAVCIV LTICELCYLI CHRVLRGLHK DKPRGGCSPS SSASRASTCR
CHHKLVEAGE VDPDPGNNKL QASAPNLTPI *

speed

0.35 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: 7.42134676579017e-08 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM090826)
known disease mutation: rs6492 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr1:35250860A>GN/A show variant in all transcripts IGV

HGNC symbol

GJB3

Ensembl transcript ID

ENST00000373362

Genbank transcript ID

NM_001005752

UniProt peptide

O75712

alteration type

single base exchange

alteration region

CDS

DNA changes

c.497A>G
cDNA.687A>G
g.4071A>G

AA changes

N166S Score: 46 explain score(s)

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

166

frameshift

known variant

Reference ID: rs121908851

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

regulatory features

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	0.169	0.076
	0.012	0.086
(flanking)	0.829	0.285

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 gained	4070	0.79	mu: GTGCCAGCGTGGCCC	GCCA\|gcgt

distance from splice site

522

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

166

mutated

all conserved

166

Ptroglodytes

no homologue

Mmulatta

all identical

ENSMMUG00000022677

166

Fcatus

all identical

ENSFCAG00000014055

166

Mmusculus

all conserved

ENSMUSG00000042367

166

Ggallus

no homologue

Trubripes

no homologue

Drerio

all conserved

ENSDARG00000042866

159

Dmelanogaster

no homologue

Celegans

no homologue

Xtropicalis

all identical

ENSXETG00000016481

166

protein features

start (aa)	end (aa)	feature	details
150	187	TOPO_DOM	Extracellular (Potential).	lost
188	210	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
211	270	TOPO_DOM	Cytoplasmic (Potential).	might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

813 / 813

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

271 / 271

position of stopcodon in wt / mu cDNA

1003 / 1003

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

191 / 191

chromosome

strand

last intron/exon boundary

166

theoretical NMD boundary in CDS

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

length of CDS

813

coding sequence (CDS) position

497

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

687

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

4071

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

35250860

original gDNA sequence snippet

GCGCCTGGTGCAGTGTGCCAACGTGGCCCCCTGCCCCAACA

altered gDNA sequence snippet

GCGCCTGGTGCAGTGTGCCAGCGTGGCCCCCTGCCCCAACA

original cDNA sequence snippet

GCGCCTGGTGCAGTGTGCCAACGTGGCCCCCTGCCCCAACA

altered cDNA sequence snippet

GCGCCTGGTGCAGTGTGCCAGCGTGGCCCCCTGCCCCAACA

wildtype AA sequence

mutated AA sequence

MDWKTLQALL SGVNKYSTAF GRIWLSVVFV FRVLVYVVAA ERVWGDEQKD FDCNTKQPGC
TNVCYDNYFP ISNIRLWALQ LIFVTCPSLL VILHVAYREE RERRHRQKHG DQCAKLYDNA
GKKHGGLWWT YLFSLIFKLI IEFLFLYLLH TLWHGFNMPR LVQCASVAPC PNIVDCYIAR
PTEKKIFTYF MVGASAVCIV LTICELCYLI CHRVLRGLHK DKPRGGCSPS SSASRASTCR
CHHKLVEAGE VDPDPGNNKL QASAPNLTPI *

speed

0.35 s

MutationTaster - study a chromosomal position

Results

Taster files

mutation t@sting

Prediction

disease causing

mutation t@sting

Prediction

disease causing

Problems