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 3.509761 s

Results

genesymbol	prediction	probability	model	prediction problem	splicing	ClinVar	amino acid changes	variant type	dbSNP ID	protein length	file
GDAP1	disease_causing_automatic	0.999999961023372	simple_aae		affected	0	P231L	single base exchange	rs121908114		show file
GDAP1	disease_causing_automatic	0.999999961023372	simple_aae		affected	0	P163L	single base exchange	rs121908114		show file

Taster files

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999999961023372 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM083517)
known disease mutation: rs4202 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr8:75275286C>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.692C>T
cDNA.772C>T
g.41922C>T

AA changes

P231L Score: 98 explain score(s)

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

231

frameshift

known variant

Reference ID: rs121908114

database	homozygous (T/T)	heterozygous	allele carriers
1000G	0	4	4
ExAC	0	3	3

known disease mutation: rs4202 (pathogenic for Charcot-Marie-Tooth disease, type 4A|Charcot-Marie-Tooth disease type 2K|Charcot-Marie-Tooth disease|not provided) dbSNP NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM083517)

known disease mutation at this position, please check HGMD for details (HGMD ID CM083517)
known disease mutation at this position, please check HGMD for details (HGMD ID CM083517)

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	5.429	1
	3.408	1
(flanking)	1.466	1

explain score(s) and/or inspect your position(s) in in UCSC Genome Browser

splice sites

alteration within used splice site, likely to disturb normal splicing

effect	gDNA position	score	detection sequence	exon-intron border
Donor lost	41923	sequence motif lost	-	wt: CCAG\|gtag mu: CTAG.gtag
Donor marginally decreased	41923	wt: 0.9879 / mu: 0.9858 (marginal change - not scored)	wt: ACCCCAGGTAGGTTC mu: ACCCTAGGTAGGTTC	CCCA\|ggta
Donor gained	41918	0.40	mu: AAGAAACCCTAGGTA	GAAA\|ccct

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

231

mutated

not conserved

231

Ptroglodytes

all identical

ENSPTRG00000020354

231

Mmulatta

all identical

ENSMMUG00000022326

231

Fcatus

all identical

ENSFCAG00000014031

231

Mmusculus

all identical

ENSMUSG00000025777

231

Ggallus

no homologue

Trubripes

no homologue

Drerio

all identical

ENSDARG00000058601

255

Dmelanogaster

not conserved

FBgn0035587

230

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

692

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

772

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

41922

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

75275286

original gDNA sequence snippet

AAGAAGAAATGAAGAAACCCCAGGTAGGTTCTCATTTATAT

altered gDNA sequence snippet

AAGAAGAAATGAAGAAACCCTAGGTAGGTTCTCATTTATAT

original cDNA sequence snippet

AAGAAGAAATGAAGAAACCCCAGAAGAGGGCCAGCAACCTT

altered cDNA sequence snippet

AAGAAGAAATGAAGAAACCCTAGAAGAGGGCCAGCAACCTT

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 LEEGQQPWLC
GESFTLADVS LAVTLHRLKF LGFARRNWGN GKRPNLETYY ERVLKRKTFN KVLGHVNNIL
ISAVLPTAFR VAKKRAPKVL GTTLVVGLLA GVGYFAFMLF RKRLGSMILA FRPRPNYF*

speed

0.65 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: 0.999999961023372 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM083517)
known disease mutation: rs4202 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr8:75275286C>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.488C>T
cDNA.606C>T
g.41922C>T

AA changes

P163L Score: 98 explain score(s)

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

163

frameshift

known variant

Reference ID: rs121908114

database	homozygous (T/T)	heterozygous	allele carriers
1000G	0	4	4
ExAC	0	3	3

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	5.429	1
	3.408	1
(flanking)	1.466	1

explain score(s) and/or inspect your position(s) in in UCSC Genome Browser

splice sites

alteration within used splice site, likely to disturb normal splicing

effect	gDNA position	score	detection sequence	exon-intron border
Donor lost	41923	sequence motif lost	-	wt: CCAG\|gtag mu: CTAG.gtag
Donor marginally decreased	41923	wt: 0.9879 / mu: 0.9858 (marginal change - not scored)	wt: ACCCCAGGTAGGTTC mu: ACCCTAGGTAGGTTC	CCCA\|ggta
Donor gained	41918	0.40	mu: AAGAAACCCTAGGTA	GAAA\|ccct

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

163

mutated

not conserved

163

Ptroglodytes

all identical

ENSPTRG00000020354

231

Mmulatta

all identical

ENSMMUG00000022326

231

Fcatus

all identical

ENSFCAG00000014031

231

Mmusculus

all identical

ENSMUSG00000025777

231

Ggallus

no homologue

Trubripes

no homologue

Drerio

all identical

ENSDARG00000058601

255

Dmelanogaster

not conserved

FBgn0035587

230

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

488

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

606

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

41922

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

75275286

original gDNA sequence snippet

AAGAAGAAATGAAGAAACCCCAGGTAGGTTCTCATTTATAT

altered gDNA sequence snippet

AAGAAGAAATGAAGAAACCCTAGGTAGGTTCTCATTTATAT

original cDNA sequence snippet

AAGAAGAAATGAAGAAACCCCAGAAGAGGGCCAGCAACCTT

altered cDNA sequence snippet

AAGAAGAAATGAAGAAACCCTAGAAGAGGGCCAGCAACCTT

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 ETLEEGQQPW LCGESFTLAD
VSLAVTLHRL KFLGFARRNW GNGKRPNLET YYERVLKRKT FNKVLGHVNN ILISAVLPTA
FRVAKKRAPK VLGTTLVVGL LAGVGYFAFM LFRKRLGSMI LAFRPRPNYF *

speed

0.85 s

MutationTaster - study a chromosomal position

Results

Taster files

mutation t@sting

Prediction

disease causing

mutation t@sting

Prediction

disease causing

Problems