MutationTaster - study a chromosomal position

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input seems to be ok - now mapping the variant to the different transcripts...
found 3 transcript(s)...
Querying Taster for transcript #1: ENST00000373176
Querying Taster for transcript #2: ENST00000373156
Querying Taster for transcript #3: ENST00000223836
MT speed 0 s - this script 3.910935 s

Results

genesymbol	prediction	probability	model	prediction problem	splicing	ClinVar	amino acid changes	variant type	dbSNP ID	protein length	file
AK1	disease_causing_automatic	0.999999999702629	simple_aae		affected	0	Y164C	single base exchange	rs137853203		show file
AK1	disease_causing_automatic	0.999999999702629	simple_aae		affected	0	Y164C	single base exchange	rs137853203		show file
AK1	disease_causing_automatic	0.999999999702629	simple_aae		affected	0	Y180C	single base exchange	rs137853203		show file

Taster files

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999999999702629 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM970075)
known disease mutation: rs18265 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr9:130630625T>CN/A show variant in all transcripts IGV

HGNC symbol

AK1

Ensembl transcript ID

ENST00000373176

Genbank transcript ID

NM_000476

UniProt peptide

P00568

alteration type

single base exchange

alteration region

CDS

DNA changes

c.491A>G
cDNA.644A>G
g.9398A>G

AA changes

Y164C Score: 194 explain score(s)

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

164

frameshift

known variant

Reference ID: rs137853203
Allele 'C' was neither found in ExAC nor 1000G.
known disease mutation: rs18265 (pathogenic for Adenylate kinase deficiency, hemolytic anemia due to) dbSNP NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM970075)

known disease mutation at this position, please check HGMD for details (HGMD ID CM970075)
known disease mutation at this position, please check HGMD for details (HGMD ID CM970075)

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	0.083	0.997
	4.365	1
(flanking)	4.365	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 marginally increased	9399	wt: 0.8566 / mu: 0.8622 (marginal change - not scored)	wt: GAACCTGTCATCGCCTTCTATGAGAAACGTGGCATTGTGCG mu: GAACCTGTCATCGCCTTCTGTGAGAAACGTGGCATTGTGCG	ctat\|GAGA
Acc increased	9397	wt: 0.47 / mu: 0.83	wt: CAGAACCTGTCATCGCCTTCTATGAGAAACGTGGCATTGTG mu: CAGAACCTGTCATCGCCTTCTGTGAGAAACGTGGCATTGTG	ttct\|ATGA

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

164

mutated

not conserved

164

Ptroglodytes

all identical

ENSPTRG00000021402

164

Mmulatta

all identical

ENSMMUG00000013998

180

Fcatus

no homologue

Mmusculus

all identical

ENSMUSG00000026817

180

Ggallus

no homologue

Trubripes

all identical

ENSTRUG00000006830

181

Drerio

all identical

ENSDARG00000001950

164

Dmelanogaster

all identical

FBgn0022709

188

Celegans

all identical

F38B2.4

177

Xtropicalis

all identical

ENSXETG00000021999

531

protein features

start (aa)	end (aa)	feature	details
158	167	HELIX		lost
170	174	STRAND		might get lost (downstream of altered splice site)
179	193	HELIX		might get lost (downstream of altered splice site)
181	181	CONFLICT	S -> E (in Ref. 1; AA sequence).	might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

585 / 585

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

195 / 195

position of stopcodon in wt / mu cDNA

738 / 738

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

154 / 154

chromosome

strand

-1

last intron/exon boundary

670

theoretical NMD boundary in CDS

466

length of CDS

585

coding sequence (CDS) position

491

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

644

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

9398

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

130630625

original gDNA sequence snippet

AGAACCTGTCATCGCCTTCTATGAGAAACGTGGCATTGTGC

altered gDNA sequence snippet

AGAACCTGTCATCGCCTTCTGTGAGAAACGTGGCATTGTGC

original cDNA sequence snippet

AGAACCTGTCATCGCCTTCTATGAGAAACGTGGCATTGTGC

altered cDNA sequence snippet

AGAACCTGTCATCGCCTTCTGTGAGAAACGTGGCATTGTGC

wildtype AA sequence

MEEKLKKTKI IFVVGGPGSG KGTQCEKIVQ KYGYTHLSTG DLLRSEVSSG SARGKKLSEI
MEKGQLVPLE TVLDMLRDAM VAKVNTSKGF LIDGYPREVQ QGEEFERRIG QPTLLLYVDA
GPETMTQRLL KRGETSGRVD DNEETIKKRL ETYYKATEPV IAFYEKRGIV RKVNAEGSVD
SVFSQVCTHL DALK*

mutated AA sequence

speed

1.00 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: 0.999999999702629 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM970075)
known disease mutation: rs18265 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr9:130630625T>CN/A show variant in all transcripts IGV

HGNC symbol

AK1

Ensembl transcript ID

ENST00000373156

Genbank transcript ID

N/A

UniProt peptide

P00568

alteration type

single base exchange

alteration region

CDS

DNA changes

c.491A>G
cDNA.654A>G
g.9398A>G

AA changes

Y164C Score: 194 explain score(s)

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

164

frameshift

known variant

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	0.083	0.997
	4.365	1
(flanking)	4.365	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 marginally increased	9399	wt: 0.8566 / mu: 0.8622 (marginal change - not scored)	wt: GAACCTGTCATCGCCTTCTATGAGAAACGTGGCATTGTGCG mu: GAACCTGTCATCGCCTTCTGTGAGAAACGTGGCATTGTGCG	ctat\|GAGA
Acc increased	9397	wt: 0.47 / mu: 0.83	wt: CAGAACCTGTCATCGCCTTCTATGAGAAACGTGGCATTGTG mu: CAGAACCTGTCATCGCCTTCTGTGAGAAACGTGGCATTGTG	ttct\|ATGA

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

164

mutated

not conserved

164

Ptroglodytes

all identical

ENSPTRG00000021402

164

Mmulatta

all identical

ENSMMUG00000013998

180

Fcatus

no homologue

Mmusculus

all identical

ENSMUSG00000026817

180

Ggallus

no homologue

Trubripes

all identical

ENSTRUG00000006830

181

Drerio

all identical

ENSDARG00000001950

164

Dmelanogaster

all identical

FBgn0022709

188

Celegans

all identical

F38B2.4

177

Xtropicalis

all identical

ENSXETG00000021999

531

protein features

start (aa)	end (aa)	feature	details
158	167	HELIX		lost
170	174	STRAND		might get lost (downstream of altered splice site)
179	193	HELIX		might get lost (downstream of altered splice site)
181	181	CONFLICT	S -> E (in Ref. 1; AA sequence).	might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

585 / 585

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

195 / 195

position of stopcodon in wt / mu cDNA

748 / 748

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

164 / 164

chromosome

strand

-1

last intron/exon boundary

680

theoretical NMD boundary in CDS

466

length of CDS

585

coding sequence (CDS) position

491

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

654

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

9398

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

130630625

original gDNA sequence snippet

AGAACCTGTCATCGCCTTCTATGAGAAACGTGGCATTGTGC

altered gDNA sequence snippet

AGAACCTGTCATCGCCTTCTGTGAGAAACGTGGCATTGTGC

original cDNA sequence snippet

AGAACCTGTCATCGCCTTCTATGAGAAACGTGGCATTGTGC

altered cDNA sequence snippet

AGAACCTGTCATCGCCTTCTGTGAGAAACGTGGCATTGTGC

wildtype AA sequence

mutated AA sequence

speed

1.05 s

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999999999702629 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM970075)
known disease mutation: rs18265 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr9:130630625T>CN/A show variant in all transcripts IGV

HGNC symbol

AK1

Ensembl transcript ID

ENST00000223836

Genbank transcript ID

N/A

UniProt peptide

P00568

alteration type

single base exchange

alteration region

CDS

DNA changes

c.539A>G
cDNA.635A>G
g.9398A>G

AA changes

Y180C Score: 194 explain score(s)

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

180

frameshift

known variant

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	0.083	0.997
	4.365	1
(flanking)	4.365	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 marginally increased	9399	wt: 0.8566 / mu: 0.8622 (marginal change - not scored)	wt: GAACCTGTCATCGCCTTCTATGAGAAACGTGGCATTGTGCG mu: GAACCTGTCATCGCCTTCTGTGAGAAACGTGGCATTGTGCG	ctat\|GAGA
Acc increased	9397	wt: 0.47 / mu: 0.83	wt: CAGAACCTGTCATCGCCTTCTATGAGAAACGTGGCATTGTG mu: CAGAACCTGTCATCGCCTTCTGTGAGAAACGTGGCATTGTG	ttct\|ATGA

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

180

mutated

not conserved

180

Ptroglodytes

all identical

ENSPTRG00000021402

164

Mmulatta

all identical

ENSMMUG00000013998

180

Fcatus

no homologue

Mmusculus

all identical

ENSMUSG00000026817

180

Ggallus

no homologue

Trubripes

all identical

ENSTRUG00000006830

181

Drerio

all identical

ENSDARG00000001950

164

Dmelanogaster

all identical

FBgn0022709

188

Celegans

all identical

F38B2.4

177

Xtropicalis

all identical

ENSXETG00000021999

531

protein features

start (aa)	end (aa)	feature	details
179	193	HELIX		lost
181	181	CONFLICT	S -> E (in Ref. 1; AA sequence).	might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

633 / 633

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

211 / 211

position of stopcodon in wt / mu cDNA

729 / 729

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

97 / 97

chromosome

strand

-1

last intron/exon boundary

661

theoretical NMD boundary in CDS

514

length of CDS

633

coding sequence (CDS) position

539

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

635

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

9398

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

130630625

original gDNA sequence snippet

AGAACCTGTCATCGCCTTCTATGAGAAACGTGGCATTGTGC

altered gDNA sequence snippet

AGAACCTGTCATCGCCTTCTGTGAGAAACGTGGCATTGTGC

original cDNA sequence snippet

AGAACCTGTCATCGCCTTCTATGAGAAACGTGGCATTGTGC

altered cDNA sequence snippet

AGAACCTGTCATCGCCTTCTGTGAGAAACGTGGCATTGTGC

wildtype AA sequence

MGCCSSSDPR REDDLRAREK LKKTKIIFVV GGPGSGKGTQ CEKIVQKYGY THLSTGDLLR
SEVSSGSARG KKLSEIMEKG QLVPLETVLD MLRDAMVAKV NTSKGFLIDG YPREVQQGEE
FERRIGQPTL LLYVDAGPET MTQRLLKRGE TSGRVDDNEE TIKKRLETYY KATEPVIAFY
EKRGIVRKVN AEGSVDSVFS QVCTHLDALK *

mutated AA sequence

speed

0.83 s

MutationTaster - study a chromosomal position

Results

Taster files

mutation t@sting

Prediction

disease causing

mutation t@sting

Prediction

disease causing

mutation t@sting

Prediction

disease causing

Problems