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 3.059599 s

Results

genesymbol	prediction	probability	model	prediction problem	splicing	ClinVar	amino acid changes	variant type	dbSNP ID	protein length	file
GJA8	disease_causing_automatic	0.999997677084829	simple_aae		affected	0	R198Q	single base exchange	rs80358205		show file
GJA8	disease_causing_automatic	0.999997677084829	simple_aae		affected	0	R198Q	single base exchange	rs80358205		show file

Taster files

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999997677084829 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM065224)
known disease mutation: rs8726 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr1:147380675G>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.593G>A
cDNA.646G>A
g.5730G>A

AA changes

R198Q Score: 43 explain score(s)

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

198

frameshift

known variant

Reference ID: rs80358205
Allele 'A' was neither found in ExAC nor 1000G.
known disease mutation: rs8726 (pathogenic for Cataract 1) dbSNP NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM065224)

known disease mutation at this position, please check HGMD for details (HGMD ID CM065224)
known disease mutation at this position, please check HGMD for details (HGMD ID CM065224)

regulatory features

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

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	0.721	0.975
	5.784	1
(flanking)	-0.033	0.983

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	5730	wt: 0.8198 / mu: 0.8545 (marginal change - not scored)	wt: GGTGGACTGCTTCGTGTCCCGGCCCACGGAGAAAACCATCT mu: GGTGGACTGCTTCGTGTCCCAGCCCACGGAGAAAACCATCT	cccg\|GCCC
Donor increased	5734	wt: 0.45 / mu: 0.68	wt: CGGCCCACGGAGAAA mu: CAGCCCACGGAGAAA	GCCC\|acgg
Donor increased	5731	wt: 0.28 / mu: 0.70	wt: TCCCGGCCCACGGAG mu: TCCCAGCCCACGGAG	CCGG\|ccca

distance from splice site

604

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

198

mutated

all conserved

198

Ptroglodytes

all identical

ENSPTRG00000001225

198

Mmulatta

all identical

ENSMMUG00000001382

204

Fcatus

no homologue

Mmusculus

all identical

ENSMUSG00000049908

205

Ggallus

all identical

ENSGALG00000015488

200

Trubripes

no homologue

Drerio

all identical

ENSDARG00000015076

204

Dmelanogaster

no homologue

Celegans

no homologue

Xtropicalis

all identical

ENSXETG00000016305

202

protein features

start (aa)	end (aa)	feature	details
174	204	TOPO_DOM	Extracellular (Potential).	lost
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

593

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

646

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

5730

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

147380675

original gDNA sequence snippet

GGTGGACTGCTTCGTGTCCCGGCCCACGGAGAAAACCATCT

altered gDNA sequence snippet

GGTGGACTGCTTCGTGTCCCAGCCCACGGAGAAAACCATCT

original cDNA sequence snippet

GGTGGACTGCTTCGTGTCCCGGCCCACGGAGAAAACCATCT

altered cDNA sequence snippet

GGTGGACTGCTTCGTGTCCCAGCCCACGGAGAAAACCATCT

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 AEFVWGDEQS DFVCNTQQPG
CENVCYDEAF PISHIRLWVL QIIFVSTPSL MYVGHAVHYV RMEEKRKSRE AEELGQQAGT
NGGPDQGSVK KSSGSKGTKK FRLEGTLLRT YICHIIFKTL FEVGFIVGHY FLYGFRILPL
YRCSRWPCPN VVDCFVSQPT 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

1.01 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: 0.999997677084829 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM065224)
known disease mutation: rs8726 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr1:147380675G>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.593G>A
cDNA.593G>A
g.5730G>A

AA changes

R198Q Score: 43 explain score(s)

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

198

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)	0.721	0.975
	5.784	1
(flanking)	-0.033	0.983

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	5730	wt: 0.8198 / mu: 0.8545 (marginal change - not scored)	wt: GGTGGACTGCTTCGTGTCCCGGCCCACGGAGAAAACCATCT mu: GGTGGACTGCTTCGTGTCCCAGCCCACGGAGAAAACCATCT	cccg\|GCCC
Donor increased	5734	wt: 0.45 / mu: 0.68	wt: CGGCCCACGGAGAAA mu: CAGCCCACGGAGAAA	GCCC\|acgg
Donor increased	5731	wt: 0.28 / mu: 0.70	wt: TCCCGGCCCACGGAG mu: TCCCAGCCCACGGAG	CCGG\|ccca

distance from splice site

593

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

198

mutated

all conserved

198

Ptroglodytes

all identical

ENSPTRG00000001225

198

Mmulatta

all identical

ENSMMUG00000001382

204

Fcatus

no homologue

Mmusculus

all identical

ENSMUSG00000049908

205

Ggallus

all identical

ENSGALG00000015488

200

Trubripes

no homologue

Drerio

all identical

ENSDARG00000015076

204

Dmelanogaster

no homologue

Celegans

no homologue

Xtropicalis

all identical

ENSXETG00000016305

202

protein features

start (aa)	end (aa)	feature	details
174	204	TOPO_DOM	Extracellular (Potential).	lost
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

593

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

593

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

5730

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

147380675

original gDNA sequence snippet

GGTGGACTGCTTCGTGTCCCGGCCCACGGAGAAAACCATCT

altered gDNA sequence snippet

GGTGGACTGCTTCGTGTCCCAGCCCACGGAGAAAACCATCT

original cDNA sequence snippet

GGTGGACTGCTTCGTGTCCCGGCCCACGGAGAAAACCATCT

altered cDNA sequence snippet

GGTGGACTGCTTCGTGTCCCAGCCCACGGAGAAAACCATCT

wildtype AA sequence

mutated AA sequence

MGDWSFLGNI LEEVNEHSTV IGRVWLTVLF IFRILILGTA AEFVWGDEQS DFVCNTQQPG
CENVCYDEAF PISHIRLWVL QIIFVSTPSL MYVGHAVHYV RMEEKRKSRE AEELGQQAGT
NGGPDQGSVK KSSGSKGTKK FRLEGTLLRT YICHIIFKTL FEVGFIVGHY FLYGFRILPL
YRCSRWPCPN VVDCFVSQPT 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

0.95 s

MutationTaster - study a chromosomal position

Results

Taster files

mutation t@sting

Prediction

disease causing

mutation t@sting

Prediction

disease causing

Problems