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: ENST00000220822
Querying Taster for transcript #2: ENST00000434412
MT speed 0 s - this script 4.799488 s

Results

genesymbol	prediction	probability	model	prediction problem	splicing	ClinVar	amino acid changes	variant type	dbSNP ID	protein length	file
GDAP1	disease_causing_automatic	0.999999799611606	simple_aae		affected	0	C240Y	single base exchange	rs121908115		show file
GDAP1	disease_causing_automatic	0.999999799611606	simple_aae		affected	0	C172Y	single base exchange	rs121908115		show file

Taster files

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999999799611606 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM095050)
known disease mutation: rs4203 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr8:75276244G>AN/A show variant in all transcripts IGV

HGNC symbol

GDAP1

Ensembl transcript ID

ENST00000220822

Genbank transcript ID

NM_018972

UniProt peptide

Q8TB36

alteration type

single base exchange

alteration region

CDS

DNA changes

c.719G>A
cDNA.799G>A
g.42880G>A

AA changes

C240Y Score: 194 explain score(s)

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

240

frameshift

known variant

Reference ID: rs121908115
Allele 'A' was neither found in ExAC nor 1000G.
known disease mutation: rs4203 (pathogenic for Charcot-Marie-Tooth disease type 2K) dbSNP NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM095050)

known disease mutation at this position, please check HGMD for details (HGMD ID CM095050)
known disease mutation at this position, please check HGMD for details (HGMD ID CM095050)

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	4.589	1
	5.539	1
(flanking)	-0.105	0.989

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	42882	wt: 0.9477 / mu: 0.9902 (marginal change - not scored)	wt: TCTGCGGTGAATCCT mu: TCTACGGTGAATCCT	TGCG\|gtga
Donor increased	42881	wt: 0.72 / mu: 0.88	wt: CTCTGCGGTGAATCC mu: CTCTACGGTGAATCC	CTGC\|ggtg

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

240

mutated

not conserved

240

Ptroglodytes

all identical

ENSPTRG00000020354

240

Mmulatta

all identical

ENSMMUG00000022326

240

Fcatus

all identical

ENSFCAG00000014031

240

Mmusculus

all identical

ENSMUSG00000025777

240

Ggallus

no homologue

Trubripes

no homologue

Drerio

all identical

ENSDARG00000058601

264

Dmelanogaster

not conserved

FBgn0035587

236

Celegans

no homologue

Xtropicalis

no homologue

protein features

start (aa)	end (aa)	feature	details
153	309	DOMAIN	GST C-terminal.	lost
292	312	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
320	340	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
320	358	REGION	Required for mitochondrial localization.	might get lost (downstream of altered splice site)
351	351	CONFLICT	F -> L (in Ref. 1; CAA76892).	might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

1077 / 1077

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

359 / 359

position of stopcodon in wt / mu cDNA

1157 / 1157

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

81 / 81

chromosome

strand

last intron/exon boundary

775

theoretical NMD boundary in CDS

644

length of CDS

1077

coding sequence (CDS) position

719

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

799

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

42880

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

75276244

original gDNA sequence snippet

GGGCCAGCAACCTTGGCTCTGCGGTGAATCCTTCACCCTGG

altered gDNA sequence snippet

GGGCCAGCAACCTTGGCTCTACGGTGAATCCTTCACCCTGG

original cDNA sequence snippet

GGGCCAGCAACCTTGGCTCTGCGGTGAATCCTTCACCCTGG

altered cDNA sequence snippet

GGGCCAGCAACCTTGGCTCTACGGTGAATCCTTCACCCTGG

wildtype AA sequence

MAERQEEQRG SPPLRAEGKA DAEVKLILYH WTHSFSSQKV RLVIAEKALK CEEHDVSLPL
SEHNEPWFMR LNSTGEVPVL IHGENIICEA TQIIDYLEQT FLDERTPRLM PDKESMYYPR
VQHYRELLDS LPMDAYTHGC ILHPELTVDS MIPAYATTRI RSQIGNTESE LKKLAEENPD
LQEAYIAKQK RLKSKLLDHD NVKYLKKILD ELEKVLDQVE TELQRRNEET PEEGQQPWLC
GESFTLADVS LAVTLHRLKF LGFARRNWGN GKRPNLETYY ERVLKRKTFN KVLGHVNNIL
ISAVLPTAFR VAKKRAPKVL GTTLVVGLLA GVGYFAFMLF RKRLGSMILA FRPRPNYF*

mutated AA sequence

MAERQEEQRG SPPLRAEGKA DAEVKLILYH WTHSFSSQKV RLVIAEKALK CEEHDVSLPL
SEHNEPWFMR LNSTGEVPVL IHGENIICEA TQIIDYLEQT FLDERTPRLM PDKESMYYPR
VQHYRELLDS LPMDAYTHGC ILHPELTVDS MIPAYATTRI RSQIGNTESE LKKLAEENPD
LQEAYIAKQK RLKSKLLDHD NVKYLKKILD ELEKVLDQVE TELQRRNEET PEEGQQPWLY
GESFTLADVS LAVTLHRLKF LGFARRNWGN GKRPNLETYY ERVLKRKTFN KVLGHVNNIL
ISAVLPTAFR VAKKRAPKVL GTTLVVGLLA GVGYFAFMLF RKRLGSMILA FRPRPNYF*

speed

1.37 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: 0.999999799611606 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM095050)
known disease mutation: rs4203 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr8:75276244G>AN/A show variant in all transcripts IGV

HGNC symbol

GDAP1

Ensembl transcript ID

ENST00000434412

Genbank transcript ID

NM_001040875

UniProt peptide

Q8TB36

alteration type

single base exchange

alteration region

CDS

DNA changes

c.515G>A
cDNA.633G>A
g.42880G>A

AA changes

C172Y Score: 194 explain score(s)

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

172

frameshift

known variant

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	4.589	1
	5.539	1
(flanking)	-0.105	0.989

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	42882	wt: 0.9477 / mu: 0.9902 (marginal change - not scored)	wt: TCTGCGGTGAATCCT mu: TCTACGGTGAATCCT	TGCG\|gtga
Donor increased	42881	wt: 0.72 / mu: 0.88	wt: CTCTGCGGTGAATCC mu: CTCTACGGTGAATCC	CTGC\|ggtg

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

172

mutated

not conserved

172

Ptroglodytes

all identical

ENSPTRG00000020354

240

Mmulatta

all identical

ENSMMUG00000022326

240

Fcatus

all identical

ENSFCAG00000014031

240

Mmusculus

all identical

ENSMUSG00000025777

240

Ggallus

no homologue

Trubripes

no homologue

Drerio

all identical

ENSDARG00000058601

264

Dmelanogaster

not conserved

FBgn0035587

239

Celegans

no homologue

Xtropicalis

no homologue

protein features

start (aa)	end (aa)	feature	details
153	309	DOMAIN	GST C-terminal.	lost
203	203	MOD_RES	N6-acetyllysine.	might get lost (downstream of altered splice site)
292	312	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
320	340	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
320	358	REGION	Required for mitochondrial localization.	might get lost (downstream of altered splice site)
351	351	CONFLICT	F -> L (in Ref. 1; CAA76892).	might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

873 / 873

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

291 / 291

position of stopcodon in wt / mu cDNA

991 / 991

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

119 / 119

chromosome

strand

last intron/exon boundary

609

theoretical NMD boundary in CDS

440

length of CDS

873

coding sequence (CDS) position

515

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

633

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

42880

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

75276244

original gDNA sequence snippet

GGGCCAGCAACCTTGGCTCTGCGGTGAATCCTTCACCCTGG

altered gDNA sequence snippet

GGGCCAGCAACCTTGGCTCTACGGTGAATCCTTCACCCTGG

original cDNA sequence snippet

GGGCCAGCAACCTTGGCTCTGCGGTGAATCCTTCACCCTGG

altered cDNA sequence snippet

GGGCCAGCAACCTTGGCTCTACGGTGAATCCTTCACCCTGG

wildtype AA sequence

MRLNSTGEVP VLIHGENIIC EATQIIDYLE QTFLDERTPR LMPDKESMYY PRVQHYRELL
DSLPMDAYTH GCILHPELTV DSMIPAYATT RIRSQIGNTE SELKKLAEEN PDLQEAYIAK
QKRLKSKLLD HDNVKYLKKI LDELEKVLDQ VETELQRRNE ETPEEGQQPW LCGESFTLAD
VSLAVTLHRL KFLGFARRNW GNGKRPNLET YYERVLKRKT FNKVLGHVNN ILISAVLPTA
FRVAKKRAPK VLGTTLVVGL LAGVGYFAFM LFRKRLGSMI LAFRPRPNYF *

mutated AA sequence

MRLNSTGEVP VLIHGENIIC EATQIIDYLE QTFLDERTPR LMPDKESMYY PRVQHYRELL
DSLPMDAYTH GCILHPELTV DSMIPAYATT RIRSQIGNTE SELKKLAEEN PDLQEAYIAK
QKRLKSKLLD HDNVKYLKKI LDELEKVLDQ VETELQRRNE ETPEEGQQPW LYGESFTLAD
VSLAVTLHRL KFLGFARRNW GNGKRPNLET YYERVLKRKT FNKVLGHVNN ILISAVLPTA
FRVAKKRAPK VLGTTLVVGL LAGVGYFAFM LFRKRLGSMI LAFRPRPNYF *

speed

1.40 s

MutationTaster - study a chromosomal position

Results

Taster files

mutation t@sting

Prediction

disease causing

mutation t@sting

Prediction

disease causing

Problems