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 2.882089 s

Results

genesymbol	prediction	probability	model	prediction problem	splicing	ClinVar	amino acid changes	variant type	dbSNP ID	protein length	file
GJB3	disease_causing_automatic	0.99999936544882	simple_aae		affected	0	G12D	single base exchange	rs74315316		show file
GJB3	disease_causing_automatic	0.99999936544882	simple_aae		affected	0	G12D	single base exchange	rs74315316		show file

Taster files

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.99999936544882 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM980931)
known disease mutation: rs6483 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr1:35250398G>AN/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.35G>A
cDNA.650G>A
g.3609G>A

AA changes

G12D Score: 94 explain score(s)

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

frameshift

known variant

Reference ID: rs74315316
Allele 'A' was neither found in ExAC nor 1000G.
known disease mutation: rs6483 (pathogenic for Erythrokeratodermia variabilis et progressiva 1) dbSNP NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM980931)

known disease mutation at this position, please check HGMD for details (HGMD ID CM980931)
known disease mutation at this position, please check HGMD for details (HGMD ID CM980931)

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)	4.439	0.997
	4.492	0.997
(flanking)	-2.614	0.009

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 increased	3610	wt: 0.45 / mu: 0.76	wt: AGCGGTGTGAACAAG mu: AGCGATGTGAACAAG	CGGT\|gtga
Donor marginally increased	3613	wt: 0.9488 / mu: 0.9728 (marginal change - not scored)	wt: GGTGTGAACAAGTAC mu: GATGTGAACAAGTAC	TGTG\|aaca
Donor marginally increased	3605	wt: 0.9907 / mu: 0.9982 (marginal change - not scored)	wt: TACTGAGCGGTGTGA mu: TACTGAGCGATGTGA	CTGA\|gcgg
Donor gained	3607	0.47	mu: CTGAGCGATGTGAAC	GAGC\|gatg

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

mutated

not conserved

Ptroglodytes

no homologue

Mmulatta

all identical

ENSMMUG00000022677

Fcatus

all identical

ENSFCAG00000014055

Mmusculus

all identical

ENSMUSG00000042367

Ggallus

no homologue

Trubripes

no homologue

Drerio

all identical

ENSDARG00000042866

Dmelanogaster

no homologue

Celegans

no homologue

Xtropicalis

all identical

ENSXETG00000016481

protein features

start (aa)	end (aa)	feature	details
1	20	TOPO_DOM	Cytoplasmic (Potential).	lost
21	40	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
41	75	TOPO_DOM	Extracellular (Potential).	might get lost (downstream of altered splice site)
76	98	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
99	126	TOPO_DOM	Cytoplasmic (Potential).	might get lost (downstream of altered splice site)
127	149	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
150	187	TOPO_DOM	Extracellular (Potential).	might get lost (downstream of altered splice site)
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

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

650

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

3609

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

35250398

original gDNA sequence snippet

ACTCCAGGCCCTACTGAGCGGTGTGAACAAGTACTCCACAG

altered gDNA sequence snippet

ACTCCAGGCCCTACTGAGCGATGTGAACAAGTACTCCACAG

original cDNA sequence snippet

ACTCCAGGCCCTACTGAGCGGTGTGAACAAGTACTCCACAG

altered cDNA sequence snippet

ACTCCAGGCCCTACTGAGCGATGTGAACAAGTACTCCACAG

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 SDVNKYSTAF 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 *

speed

0.77 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: 0.99999936544882 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM980931)
known disease mutation: rs6483 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr1:35250398G>AN/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.35G>A
cDNA.225G>A
g.3609G>A

AA changes

G12D Score: 94 explain score(s)

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

frameshift

known variant

regulatory features

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	4.439	0.997
	4.492	0.997
(flanking)	-2.614	0.009

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 increased	3610	wt: 0.45 / mu: 0.76	wt: AGCGGTGTGAACAAG mu: AGCGATGTGAACAAG	CGGT\|gtga
Donor marginally increased	3613	wt: 0.9488 / mu: 0.9728 (marginal change - not scored)	wt: GGTGTGAACAAGTAC mu: GATGTGAACAAGTAC	TGTG\|aaca
Donor marginally increased	3605	wt: 0.9907 / mu: 0.9982 (marginal change - not scored)	wt: TACTGAGCGGTGTGA mu: TACTGAGCGATGTGA	CTGA\|gcgg
Donor gained	3607	0.47	mu: CTGAGCGATGTGAAC	GAGC\|gatg

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

mutated

not conserved

Ptroglodytes

no homologue

Mmulatta

all identical

ENSMMUG00000022677

Fcatus

all identical

ENSFCAG00000014055

Mmusculus

all identical

ENSMUSG00000042367

Ggallus

no homologue

Trubripes

no homologue

Drerio

all identical

ENSDARG00000042866

Dmelanogaster

no homologue

Celegans

no homologue

Xtropicalis

all identical

ENSXETG00000016481

protein features

start (aa)	end (aa)	feature	details
1	20	TOPO_DOM	Cytoplasmic (Potential).	lost
21	40	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
41	75	TOPO_DOM	Extracellular (Potential).	might get lost (downstream of altered splice site)
76	98	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
99	126	TOPO_DOM	Cytoplasmic (Potential).	might get lost (downstream of altered splice site)
127	149	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
150	187	TOPO_DOM	Extracellular (Potential).	might get lost (downstream of altered splice site)
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

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

225

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

3609

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

35250398

original gDNA sequence snippet

ACTCCAGGCCCTACTGAGCGGTGTGAACAAGTACTCCACAG

altered gDNA sequence snippet

ACTCCAGGCCCTACTGAGCGATGTGAACAAGTACTCCACAG

original cDNA sequence snippet

ACTCCAGGCCCTACTGAGCGGTGTGAACAAGTACTCCACAG

altered cDNA sequence snippet

ACTCCAGGCCCTACTGAGCGATGTGAACAAGTACTCCACAG

wildtype AA sequence

mutated AA sequence

speed

0.70 s

MutationTaster - study a chromosomal position

Results

Taster files

mutation t@sting

Prediction

disease causing

mutation t@sting

Prediction

disease causing

Problems