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 1.7 s - this script 3.725185 s

Results

genesymbol	prediction	probability	model	prediction problem	splicing	ClinVar	amino acid changes	variant type	dbSNP ID	protein length	file
GJB2	disease_causing_automatic	0.999999989736033	simple_aae		affected	0	R184P	single base exchange	rs80338950		show file
GJB2	disease_causing_automatic	0.999999989736033	simple_aae		affected	0	R184P	single base exchange	rs80338950		show file

Taster files

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999999989736033 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM012136)
known disease mutation at this position (HGMD CM992895)
known disease mutation: rs17007 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr13:20763170C>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.551G>C
cDNA.689G>C
g.3868G>C

AA changes

R184P Score: 103 explain score(s)

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

184

frameshift

known variant

Reference ID: rs80338950

database	homozygous (G/G)	heterozygous	allele carriers
1000G	-	-	-
ExAC	0	5	5

known disease mutation: rs17007 (pathogenic for Mutilating keratoderma|Keratitis-ichthyosis-deafness syndrome, autosomal dominant|Palmoplantar keratoderma-deafness syndrome|Knuckle pads, deafness AND leukonychia syndrome|Deafness, autosomal recessive 1A|Deafness, X-linked 2|Deafness, autosomal dominant 3a|Hystrix-like ichthyosis with deafness|Nonsyndromic hearing loss and deafness|Hearing loss|none provided|not provided|Rare genetic deafness) dbSNP NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM992895)

known disease mutation at this position, please check HGMD for details (HGMD ID CM992895)
known disease mutation at this position, please check HGMD for details (HGMD ID CM012136)

known disease mutation at this position, please check HGMD for details (HGMD ID CM992895)
known disease mutation at this position, please check HGMD for details (HGMD ID CM012136)
known disease mutation at this position, please check HGMD for details (HGMD ID CM012136)

known disease mutation at this position, please check HGMD for details (HGMD ID CM992895)
known disease mutation at this position, please check HGMD for details (HGMD ID CM012136)
known disease mutation at this position, please check HGMD for details (HGMD ID CM012136)
known disease mutation at this position, please check HGMD for details (HGMD ID CM992895)

regulatory features

H3K27me3, Histone, Histone 3 Lysine 27 Tri-Methylation
H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	1.34	1
	6.248	1
(flanking)	0.532	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
Acc marginally increased	3868	wt: 0.8897 / mu: 0.9078 (marginal change - not scored)	wt: TGTGGACTGCTTTGTGTCCCGGCCCACGGAGAAGACTGTCT mu: TGTGGACTGCTTTGTGTCCCCGCCCACGGAGAAGACTGTCT	cccg\|GCCC
Acc marginally increased	3869	wt: 0.2905 / mu: 0.3199 (marginal change - not scored)	wt: GTGGACTGCTTTGTGTCCCGGCCCACGGAGAAGACTGTCTT mu: GTGGACTGCTTTGTGTCCCCGCCCACGGAGAAGACTGTCTT	ccgg\|CCCA
Acc increased	3876	wt: 0.43 / mu: 0.74	wt: GCTTTGTGTCCCGGCCCACGGAGAAGACTGTCTTCACAGTG mu: GCTTTGTGTCCCCGCCCACGGAGAAGACTGTCTTCACAGTG	acgg\|AGAA
Acc increased	3874	wt: 0.83 / mu: 0.92	wt: CTGCTTTGTGTCCCGGCCCACGGAGAAGACTGTCTTCACAG mu: CTGCTTTGTGTCCCCGCCCACGGAGAAGACTGTCTTCACAG	ccac\|GGAG
Acc marginally increased	3862	wt: 0.9068 / mu: 0.9128 (marginal change - not scored)	wt: CAACACTGTGGACTGCTTTGTGTCCCGGCCCACGGAGAAGA mu: CAACACTGTGGACTGCTTTGTGTCCCCGCCCACGGAGAAGA	ttgt\|GTCC
Donor increased	3869	wt: 0.28 / mu: 0.68	wt: TCCCGGCCCACGGAG mu: TCCCCGCCCACGGAG	CCGG\|ccca
Acc gained	3872	0.55	mu: GACTGCTTTGTGTCCCCGCCCACGGAGAAGACTGTCTTCAC	gccc\|ACGG
Acc gained	3870	0.33	mu: TGGACTGCTTTGTGTCCCCGCCCACGGAGAAGACTGTCTTC	ccgc\|CCAC

distance from splice site

573

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

184

mutated

not conserved

184

Ptroglodytes

all identical

ENSPTRG00000031248

184

Mmulatta

all identical

ENSMMUG00000010522

184

Fcatus

all identical

ENSFCAG00000006961

184

Mmusculus

all identical

ENSMUSG00000046352

184

Ggallus

all identical

ENSGALG00000017136

184

Trubripes

no homologue

Drerio

all identical

ENSDARG00000042707

186

Dmelanogaster

no homologue

Celegans

no homologue

Xtropicalis

all identical

ENSXETG00000026112

183

protein features

start (aa)	end (aa)	feature	details
155	192	TOPO_DOM	Extracellular (Potential).	lost
185	215	HELIX		might get lost (downstream of altered splice site)
193	215	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
216	226	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

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

551

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

689

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

3868

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

20763170

original gDNA sequence snippet

TGTGGACTGCTTTGTGTCCCGGCCCACGGAGAAGACTGTCT

altered gDNA sequence snippet

TGTGGACTGCTTTGTGTCCCCGCCCACGGAGAAGACTGTCT

original cDNA sequence snippet

TGTGGACTGCTTTGTGTCCCGGCCCACGGAGAAGACTGTCT

altered cDNA sequence snippet

TGTGGACTGCTTTGTGTCCCCGCCCACGGAGAAGACTGTCT

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

speed

1.10 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: 0.999999989736033 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM012136)
known disease mutation at this position (HGMD CM992895)
known disease mutation: rs17007 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr13:20763170C>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.551G>C
cDNA.750G>C
g.3868G>C

AA changes

R184P Score: 103 explain score(s)

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

184

frameshift

known variant

Reference ID: rs80338950

database	homozygous (G/G)	heterozygous	allele carriers
1000G	-	-	-
ExAC	0	5	5

regulatory features

H3K27me3, Histone, Histone 3 Lysine 27 Tri-Methylation
H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	1.34	1
	6.248	1
(flanking)	0.532	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
Acc marginally increased	3868	wt: 0.8897 / mu: 0.9078 (marginal change - not scored)	wt: TGTGGACTGCTTTGTGTCCCGGCCCACGGAGAAGACTGTCT mu: TGTGGACTGCTTTGTGTCCCCGCCCACGGAGAAGACTGTCT	cccg\|GCCC
Acc marginally increased	3869	wt: 0.2905 / mu: 0.3199 (marginal change - not scored)	wt: GTGGACTGCTTTGTGTCCCGGCCCACGGAGAAGACTGTCTT mu: GTGGACTGCTTTGTGTCCCCGCCCACGGAGAAGACTGTCTT	ccgg\|CCCA
Acc increased	3876	wt: 0.43 / mu: 0.74	wt: GCTTTGTGTCCCGGCCCACGGAGAAGACTGTCTTCACAGTG mu: GCTTTGTGTCCCCGCCCACGGAGAAGACTGTCTTCACAGTG	acgg\|AGAA
Acc increased	3874	wt: 0.83 / mu: 0.92	wt: CTGCTTTGTGTCCCGGCCCACGGAGAAGACTGTCTTCACAG mu: CTGCTTTGTGTCCCCGCCCACGGAGAAGACTGTCTTCACAG	ccac\|GGAG
Acc marginally increased	3862	wt: 0.9068 / mu: 0.9128 (marginal change - not scored)	wt: CAACACTGTGGACTGCTTTGTGTCCCGGCCCACGGAGAAGA mu: CAACACTGTGGACTGCTTTGTGTCCCCGCCCACGGAGAAGA	ttgt\|GTCC
Donor increased	3869	wt: 0.28 / mu: 0.68	wt: TCCCGGCCCACGGAG mu: TCCCCGCCCACGGAG	CCGG\|ccca
Acc gained	3872	0.55	mu: GACTGCTTTGTGTCCCCGCCCACGGAGAAGACTGTCTTCAC	gccc\|ACGG
Acc gained	3870	0.33	mu: TGGACTGCTTTGTGTCCCCGCCCACGGAGAAGACTGTCTTC	ccgc\|CCAC

distance from splice site

750

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

184

mutated

not conserved

184

Ptroglodytes

all identical

ENSPTRG00000031248

184

Mmulatta

all identical

ENSMMUG00000010522

184

Fcatus

all identical

ENSFCAG00000006961

184

Mmusculus

all identical

ENSMUSG00000046352

184

Ggallus

all identical

ENSGALG00000017136

184

Trubripes

no homologue

Drerio

all identical

ENSDARG00000042707

186

Dmelanogaster

no homologue

Celegans

no homologue

Xtropicalis

all identical

ENSXETG00000026112

183

protein features

start (aa)	end (aa)	feature	details
155	192	TOPO_DOM	Extracellular (Potential).	lost
185	215	HELIX		might get lost (downstream of altered splice site)
193	215	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
216	226	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

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

551

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

750

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

3868

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

20763170

original gDNA sequence snippet

TGTGGACTGCTTTGTGTCCCGGCCCACGGAGAAGACTGTCT

altered gDNA sequence snippet

TGTGGACTGCTTTGTGTCCCCGCCCACGGAGAAGACTGTCT

original cDNA sequence snippet

TGTGGACTGCTTTGTGTCCCGGCCCACGGAGAAGACTGTCT

altered cDNA sequence snippet

TGTGGACTGCTTTGTGTCCCCGCCCACGGAGAAGACTGTCT

wildtype AA sequence

mutated AA sequence

speed

0.60 s

MutationTaster - study a chromosomal position

Results

Taster files

mutation t@sting

Prediction

disease causing

mutation t@sting

Prediction

disease causing

Problems