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 2.980462 s

Results

genesymbol	prediction	probability	model	prediction problem	splicing	ClinVar	amino acid changes	variant type	dbSNP ID	protein length	file
GDAP1	disease_causing_automatic	0.999813486961111	simple_aae		affected	0	R120W	single base exchange	rs104894078		show file
GDAP1	disease_causing_automatic	0.999887674899085	simple_aae		affected	0	R52W	single base exchange	rs104894078		show file

Taster files

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999813486961111 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM032927)
known disease mutation at this position (HGMD CM128292)
known disease mutation: rs4198 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr8:75272419C>TN/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.358C>T
cDNA.438C>T
g.39055C>T

AA changes

R120W Score: 101 explain score(s)

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

120

frameshift

known variant

Reference ID: rs104894078
Allele 'T' was neither found in ExAC nor 1000G.
known disease mutation: rs4198 (pathogenic for Charcot-Marie-Tooth disease, type 4A|Charcot-Marie-Tooth disease type 2K|Charcot-Marie-Tooth disease, recessive intermediate A|Charcot-Marie-Tooth disease|not provided) dbSNP NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM032927)

known disease mutation at this position, please check HGMD for details (HGMD ID CM032927)
known disease mutation at this position, please check HGMD for details (HGMD ID CM128292)

known disease mutation at this position, please check HGMD for details (HGMD ID CM032927)
known disease mutation at this position, please check HGMD for details (HGMD ID CM128292)
known disease mutation at this position, please check HGMD for details (HGMD ID CM032927)

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	0.453	1
	1.215	1
(flanking)	5.73	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 increased	39057	wt: 0.63 / mu: 0.74	wt: GAAAGCATGTATTACCCACGGGTACAACATTACCGAGAGCT mu: GAAAGCATGTATTACCCATGGGTACAACATTACCGAGAGCT	acgg\|GTAC

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

120

mutated

not conserved

120

Ptroglodytes

all identical

ENSPTRG00000020354

120

Mmulatta

all identical

ENSMMUG00000022326

120

Fcatus

all identical

ENSFCAG00000014031

120

Mmusculus

all identical

ENSMUSG00000025777

120

Ggallus

no homologue

Trubripes

no homologue

Drerio

all identical

ENSDARG00000058601

144

Dmelanogaster

all conserved

FBgn0035587

120

Celegans

no homologue

Xtropicalis

no homologue

protein features

start (aa)	end (aa)	feature	details
120	120	MUTAGEN	R->W: No effect on mitochondrial localization.	lost
153	309	DOMAIN	GST C-terminal.	might get lost (downstream of altered splice site)
157	157	MUTAGEN	T->P: No effect on mitochondrial localization.	might get lost (downstream of altered splice site)
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

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

358

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

438

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

39055

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

75272419

original gDNA sequence snippet

AAGAAAGCATGTATTACCCACGGGTACAACATTACCGAGAG

altered gDNA sequence snippet

AAGAAAGCATGTATTACCCATGGGTACAACATTACCGAGAG

original cDNA sequence snippet

AAGAAAGCATGTATTACCCACGGGTACAACATTACCGAGAG

altered cDNA sequence snippet

AAGAAAGCATGTATTACCCATGGGTACAACATTACCGAGAG

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 PDKESMYYPW
VQHYRELLDS LPMDAYTHGC ILHPELTVDS MIPAYATTRI RSQIGNTESE LKKLAEENPD
LQEAYIAKQK RLKSKLLDHD NVKYLKKILD ELEKVLDQVE TELQRRNEET PEEGQQPWLC
GESFTLADVS LAVTLHRLKF LGFARRNWGN GKRPNLETYY ERVLKRKTFN KVLGHVNNIL
ISAVLPTAFR VAKKRAPKVL GTTLVVGLLA GVGYFAFMLF RKRLGSMILA FRPRPNYF*

speed

0.44 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: 0.999887674899085 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM032927)
known disease mutation at this position (HGMD CM128292)
known disease mutation: rs4198 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr8:75272419C>TN/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.154C>T
cDNA.272C>T
g.39055C>T

AA changes

R52W Score: 101 explain score(s)

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

frameshift

known variant

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	0.453	1
	1.215	1
(flanking)	5.73	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 increased	39057	wt: 0.63 / mu: 0.74	wt: GAAAGCATGTATTACCCACGGGTACAACATTACCGAGAGCT mu: GAAAGCATGTATTACCCATGGGTACAACATTACCGAGAGCT	acgg\|GTAC

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

all identical

ENSPTRG00000020354

120

Mmulatta

all identical

ENSMMUG00000022326

120

Fcatus

all identical

ENSFCAG00000014031

120

Mmusculus

all identical

ENSMUSG00000025777

120

Ggallus

no homologue

Trubripes

no homologue

Drerio

all identical

ENSDARG00000058601

144

Dmelanogaster

all conserved

FBgn0035587

122

Celegans

no homologue

Xtropicalis

no homologue

protein features

start (aa)	end (aa)	feature	details
24	105	DOMAIN	GST N-terminal.	lost
53	53	CONFLICT	E -> G (in Ref. 1; CAA76892).	might get lost (downstream of altered splice site)
116	116	MUTAGEN	M->H: Impairment in the ability to induce mitochodrial fragmentation.	might get lost (downstream of altered splice site)
120	120	MUTAGEN	R->W: No effect on mitochondrial localization.	might get lost (downstream of altered splice site)
153	309	DOMAIN	GST C-terminal.	might get lost (downstream of altered splice site)
157	157	MUTAGEN	T->P: No effect on mitochondrial localization.	might get lost (downstream of altered splice site)
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

154

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

272

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

39055

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

75272419

original gDNA sequence snippet

AAGAAAGCATGTATTACCCACGGGTACAACATTACCGAGAG

altered gDNA sequence snippet

AAGAAAGCATGTATTACCCATGGGTACAACATTACCGAGAG

original cDNA sequence snippet

AAGAAAGCATGTATTACCCACGGGTACAACATTACCGAGAG

altered cDNA sequence snippet

AAGAAAGCATGTATTACCCATGGGTACAACATTACCGAGAG

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 PWVQHYRELL
DSLPMDAYTH GCILHPELTV DSMIPAYATT RIRSQIGNTE SELKKLAEEN PDLQEAYIAK
QKRLKSKLLD HDNVKYLKKI LDELEKVLDQ VETELQRRNE ETPEEGQQPW LCGESFTLAD
VSLAVTLHRL KFLGFARRNW GNGKRPNLET YYERVLKRKT FNKVLGHVNN ILISAVLPTA
FRVAKKRAPK VLGTTLVVGL LAGVGYFAFM LFRKRLGSMI LAFRPRPNYF *

speed

0.89 s

MutationTaster - study a chromosomal position

Results

Taster files

mutation t@sting

Prediction

disease causing

mutation t@sting

Prediction

disease causing

Problems