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: ENST00000369235
Querying Taster for transcript #2: ENST00000240986
MT speed 0 s - this script 4.697751 s

Results

genesymbol	prediction	probability	model	prediction problem	splicing	ClinVar	amino acid changes	variant type	dbSNP ID	protein length	file
GJA8	disease_causing_automatic	0.999999970896227	simple_aae		affected	0	D47N	single base exchange	rs121434643		show file
GJA8	disease_causing_automatic	0.999999970896227	simple_aae		affected	0	D47N	single base exchange	rs121434643		show file

Taster files

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999999970896227 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM081296)
known disease mutation at this position (HGMD CM082793)
known disease mutation at this position (HGMD CM132729)
known disease mutation: rs8727 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr1:147380221G>AN/A show variant in all transcripts IGV

HGNC symbol

GJA8

Ensembl transcript ID

ENST00000369235

Genbank transcript ID

N/A

UniProt peptide

P48165

alteration type

single base exchange

alteration region

CDS

DNA changes

c.139G>A
cDNA.139G>A
g.5276G>A

AA changes

D47N Score: 23 explain score(s)

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

frameshift

known variant

Reference ID: rs121434643
Allele 'A' was neither found in ExAC nor 1000G.
known disease mutation: rs8727 (pathogenic for Cataract 1) dbSNP NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM081296)

known disease mutation at this position, please check HGMD for details (HGMD ID CM081296)
known disease mutation at this position, please check HGMD for details (HGMD ID CM082793)

known disease mutation at this position, please check HGMD for details (HGMD ID CM081296)
known disease mutation at this position, please check HGMD for details (HGMD ID CM082793)
known disease mutation at this position, please check HGMD for details (HGMD ID CM132729)

known disease mutation at this position, please check HGMD for details (HGMD ID CM081296)
known disease mutation at this position, please check HGMD for details (HGMD ID CM082793)
known disease mutation at this position, please check HGMD for details (HGMD ID CM132729)
known disease mutation at this position, please check HGMD for details (HGMD ID CM081296)

known disease mutation at this position, please check HGMD for details (HGMD ID CM081296)
known disease mutation at this position, please check HGMD for details (HGMD ID CM082793)
known disease mutation at this position, please check HGMD for details (HGMD ID CM132729)
known disease mutation at this position, please check HGMD for details (HGMD ID CM081296)
known disease mutation at this position, please check HGMD for details (HGMD ID CM082793)

regulatory features

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

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	-0.207	0.978
	5.834	1
(flanking)	4.817	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
Donor marginally increased	5273	wt: 0.4683 / mu: 0.4720 (marginal change - not scored)	wt: TGTGGGGGGATGAGC mu: TGTGGGGGAATGAGC	TGGG\|ggga
Donor increased	5280	wt: 0.38 / mu: 0.72	wt: GGATGAGCAATCCGA mu: GAATGAGCAATCCGA	ATGA\|gcaa

distance from splice site

139

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

mutated

all conserved

Ptroglodytes

all identical

ENSPTRG00000001225

Mmulatta

all identical

ENSMMUG00000001382

Fcatus

no homologue

Mmusculus

all identical

ENSMUSG00000049908

Ggallus

all identical

ENSGALG00000015488

Trubripes

no homologue

Drerio

all identical

ENSDARG00000015076

Dmelanogaster

no homologue

Celegans

no homologue

Xtropicalis

all identical

ENSXETG00000016305

protein features

start (aa)	end (aa)	feature	details
47	76	TOPO_DOM	Extracellular (Potential).	lost
77	99	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
100	150	TOPO_DOM	Cytoplasmic (Potential).	might get lost (downstream of altered splice site)
110	111	CONFLICT	EA -> D (in Ref. 1; AAA77062).	might get lost (downstream of altered splice site)
151	173	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
174	204	TOPO_DOM	Extracellular (Potential).	might get lost (downstream of altered splice site)
205	227	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
228	433	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

1302 / 1302

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

434 / 434

position of stopcodon in wt / mu cDNA

1302 / 1302

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

1 / 1

chromosome

strand

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

1302

coding sequence (CDS) position

139

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

139

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

5276

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

147380221

original gDNA sequence snippet

CCGCAGAGTTCGTGTGGGGGGATGAGCAATCCGACTTCGTG

altered gDNA sequence snippet

CCGCAGAGTTCGTGTGGGGGAATGAGCAATCCGACTTCGTG

original cDNA sequence snippet

CCGCAGAGTTCGTGTGGGGGGATGAGCAATCCGACTTCGTG

altered cDNA sequence snippet

CCGCAGAGTTCGTGTGGGGGAATGAGCAATCCGACTTCGTG

wildtype AA sequence

MGDWSFLGNI LEEVNEHSTV IGRVWLTVLF IFRILILGTA AEFVWGDEQS DFVCNTQQPG
CENVCYDEAF PISHIRLWVL QIIFVSTPSL MYVGHAVHYV RMEEKRKSRE AEELGQQAGT
NGGPDQGSVK KSSGSKGTKK FRLEGTLLRT YICHIIFKTL FEVGFIVGHY FLYGFRILPL
YRCSRWPCPN VVDCFVSRPT EKTIFILFML SVASVSLFLN VMELGHLGLK GIRSALKRPV
EQPLGEIPEK SLHSIAVSSI QKAKGYQLLE EEKIVSHYFP LTEVGMVETS PLPAKPFNQF
EEKISTGPLG DLSRGYQETL PSYAQVGAQE VEGEGPPAEE GAEPEVGEKK EEAERLTTEE
QEKVAVPEGE KVETPGVDKE GEKEEPQSEK VSKQGLPAEK TPSLCPELTT DDARPLSRLS
KASSRARSDD LTV*

mutated AA sequence

MGDWSFLGNI LEEVNEHSTV IGRVWLTVLF IFRILILGTA AEFVWGNEQS DFVCNTQQPG
CENVCYDEAF PISHIRLWVL QIIFVSTPSL MYVGHAVHYV RMEEKRKSRE AEELGQQAGT
NGGPDQGSVK KSSGSKGTKK FRLEGTLLRT YICHIIFKTL FEVGFIVGHY FLYGFRILPL
YRCSRWPCPN VVDCFVSRPT EKTIFILFML SVASVSLFLN VMELGHLGLK GIRSALKRPV
EQPLGEIPEK SLHSIAVSSI QKAKGYQLLE EEKIVSHYFP LTEVGMVETS PLPAKPFNQF
EEKISTGPLG DLSRGYQETL PSYAQVGAQE VEGEGPPAEE GAEPEVGEKK EEAERLTTEE
QEKVAVPEGE KVETPGVDKE GEKEEPQSEK VSKQGLPAEK TPSLCPELTT DDARPLSRLS
KASSRARSDD LTV*

speed

1.35 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: 0.999999970896227 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM081296)
known disease mutation at this position (HGMD CM082793)
known disease mutation at this position (HGMD CM132729)
known disease mutation: rs8727 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr1:147380221G>AN/A show variant in all transcripts IGV

HGNC symbol

GJA8

Ensembl transcript ID

ENST00000240986

Genbank transcript ID

NM_005267

UniProt peptide

P48165

alteration type

single base exchange

alteration region

CDS

DNA changes

c.139G>A
cDNA.192G>A
g.5276G>A

AA changes

D47N Score: 23 explain score(s)

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

frameshift

known variant

regulatory features

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

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	-0.207	0.978
	5.834	1
(flanking)	4.817	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
Donor marginally increased	5273	wt: 0.4683 / mu: 0.4720 (marginal change - not scored)	wt: TGTGGGGGGATGAGC mu: TGTGGGGGAATGAGC	TGGG\|ggga
Donor increased	5280	wt: 0.38 / mu: 0.72	wt: GGATGAGCAATCCGA mu: GAATGAGCAATCCGA	ATGA\|gcaa

distance from splice site

150

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

mutated

all conserved

Ptroglodytes

all identical

ENSPTRG00000001225

Mmulatta

all identical

ENSMMUG00000001382

Fcatus

no homologue

Mmusculus

all identical

ENSMUSG00000049908

Ggallus

all identical

ENSGALG00000015488

Trubripes

no homologue

Drerio

all identical

ENSDARG00000015076

Dmelanogaster

no homologue

Celegans

no homologue

Xtropicalis

all identical

ENSXETG00000016305

protein features

start (aa)	end (aa)	feature	details
47	76	TOPO_DOM	Extracellular (Potential).	lost
77	99	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
100	150	TOPO_DOM	Cytoplasmic (Potential).	might get lost (downstream of altered splice site)
110	111	CONFLICT	EA -> D (in Ref. 1; AAA77062).	might get lost (downstream of altered splice site)
151	173	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
174	204	TOPO_DOM	Extracellular (Potential).	might get lost (downstream of altered splice site)
205	227	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
228	433	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

1302 / 1302

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

434 / 434

position of stopcodon in wt / mu cDNA

1355 / 1355

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

54 / 54

chromosome

strand

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

1302

coding sequence (CDS) position

139

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

192

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

5276

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

147380221

original gDNA sequence snippet

CCGCAGAGTTCGTGTGGGGGGATGAGCAATCCGACTTCGTG

altered gDNA sequence snippet

CCGCAGAGTTCGTGTGGGGGAATGAGCAATCCGACTTCGTG

original cDNA sequence snippet

CCGCAGAGTTCGTGTGGGGGGATGAGCAATCCGACTTCGTG

altered cDNA sequence snippet

CCGCAGAGTTCGTGTGGGGGAATGAGCAATCCGACTTCGTG

wildtype AA sequence

mutated AA sequence

speed

1.29 s

MutationTaster - study a chromosomal position

Results

Taster files

mutation t@sting

Prediction

disease causing

mutation t@sting

Prediction

disease causing

Problems