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: ENST00000264276
Querying Taster for transcript #2: ENST00000467448
MT speed 1.72 s - this script 3.756037 s

Results

genesymbol	prediction	probability	model	prediction problem	splicing	ClinVar	amino acid changes	variant type	dbSNP ID	protein length	file
ALS2	disease_causing_automatic	0.999999999732293	simple_aae		affected	0	C157Y	single base exchange	rs121908138		show file
ALS2	disease_causing_automatic	0.999999999986834	simple_aae		affected	0	C157Y	single base exchange	rs121908138		show file

Taster files

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999999999732293 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM061636)
known disease mutation: rs4415 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr2:202626247C>TN/A show variant in all transcripts IGV

HGNC symbol

ALS2

Ensembl transcript ID

ENST00000264276

Genbank transcript ID

NM_020919

UniProt peptide

Q96Q42

alteration type

single base exchange

alteration region

CDS

DNA changes

c.470G>A
cDNA.843G>A
g.19666G>A

AA changes

C157Y Score: 194 explain score(s)

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

157

frameshift

known variant

Reference ID: rs121908138
Allele 'T' was neither found in ExAC nor 1000G.
known disease mutation: rs4415 (pathogenic for Infantile-onset ascending hereditary spastic paralysis|not provided) dbSNP NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM061636)

known disease mutation at this position, please check HGMD for details (HGMD ID CM061636)
known disease mutation at this position, please check HGMD for details (HGMD ID CM061636)

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	0.796	1
	6	1
(flanking)	4.969	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
Donor increased	19668	wt: 0.41 / mu: 0.85	wt: CGTGTGGCGAGGAGC mu: CGTATGGCGAGGAGC	TGTG\|gcga
Donor increased	19667	wt: 0.49 / mu: 0.74	wt: GCGTGTGGCGAGGAG mu: GCGTATGGCGAGGAG	GTGT\|ggcg
Donor marginally increased	19670	wt: 0.9582 / mu: 0.9810 (marginal change - not scored)	wt: TGTGGCGAGGAGCAC mu: TATGGCGAGGAGCAC	TGGC\|gagg

distance from splice site

295

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

157

mutated

not conserved

157

Ptroglodytes

all identical

ENSPTRG00000012811

157

Mmulatta

no homologue

Fcatus

all identical

ENSFCAG00000004007

157

Mmusculus

all identical

ENSMUSG00000026024

157

Ggallus

all identical

ENSGALG00000008415

157

Trubripes

all identical

ENSTRUG00000009974

150

Drerio

all identical

ENSDARG00000076924

152

Dmelanogaster

no alignment

FBgn0037116

n/a

Celegans

no homologue

Xtropicalis

all identical

ENSXETG00000012406

155

protein features

start (aa)	end (aa)	feature	details
109	167	REPEAT	RCC1 2.	lost
169	218	REPEAT	RCC1 3.	might get lost (downstream of altered splice site)
483	483	MOD_RES	Phosphoserine.	might get lost (downstream of altered splice site)
492	492	MOD_RES	Phosphoserine.	might get lost (downstream of altered splice site)
525	576	REPEAT	RCC1 4.	might get lost (downstream of altered splice site)
533	533	MOD_RES	N6-acetyllysine.	might get lost (downstream of altered splice site)
578	627	REPEAT	RCC1 5.	might get lost (downstream of altered splice site)
690	885	DOMAIN	DH.	might get lost (downstream of altered splice site)
901	1007	DOMAIN	PH.	might get lost (downstream of altered splice site)
1049	1071	REPEAT	MORN 1.	might get lost (downstream of altered splice site)
1072	1094	REPEAT	MORN 2.	might get lost (downstream of altered splice site)
1100	1122	REPEAT	MORN 3.	might get lost (downstream of altered splice site)
1123	1145	REPEAT	MORN 4.	might get lost (downstream of altered splice site)
1151	1173	REPEAT	MORN 5.	might get lost (downstream of altered splice site)
1175	1197	REPEAT	MORN 6.	might get lost (downstream of altered splice site)
1198	1220	REPEAT	MORN 7.	might get lost (downstream of altered splice site)
1221	1244	REPEAT	MORN 8.	might get lost (downstream of altered splice site)
1344	1344	MOD_RES	Phosphothreonine.	might get lost (downstream of altered splice site)
1464	1464	MOD_RES	Phosphoserine.	might get lost (downstream of altered splice site)
1513	1657	DOMAIN	VPS9.	might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

4974 / 4974

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

1658 / 1658

position of stopcodon in wt / mu cDNA

5347 / 5347

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

374 / 374

chromosome

strand

-1

last intron/exon boundary

5309

theoretical NMD boundary in CDS

4885

length of CDS

4974

coding sequence (CDS) position

470

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

843

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

19666

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

202626247

original gDNA sequence snippet

CAGGATTTTACAGTTGGCGTGTGGCGAGGAGCACACTCTGG

altered gDNA sequence snippet

CAGGATTTTACAGTTGGCGTATGGCGAGGAGCACACTCTGG

original cDNA sequence snippet

CAGGATTTTACAGTTGGCGTGTGGCGAGGAGCACACTCTGG

altered cDNA sequence snippet

CAGGATTTTACAGTTGGCGTATGGCGAGGAGCACACTCTGG

wildtype AA sequence

MDSKKRSSTE AEGSKERGLV HIWQAGSFPI TPERLPGWGG KTVLQAALGV KHGVLLTEDG
EVYSFGTLPW RSGPVEICPS SPILENALVG QYVITVATGS FHSGAVTDNG VAYMWGENSA
GQCAVANQQY VPEPNPVSIA DSEASPLLAV RILQLACGEE HTLALSISRE IWAWGTGCQL
GLITTAFPVT KPQKVEHLAG RVVLQVACGA FHSLALVQCL PSQDLKPVPE RCNQCSQLLI
TMTDKEDHVI ISDSHCCPLG VTLTESQAEN HASTALSPST ETLDRQEEVF ENTLVANDQS
VATELNAVSA QITSSDAMSS QQNVMGTTEI SSARNIPSYP DTQAVNEYLR KLSDHSVRED
SEHGEKPVPS QPLLEEAIPN LHSPPTTSTS ALNSLVVSCA SAVGVRVAAT YEAGALSLKK
VMNFYSTTPC ETGAQAGSSA IGPEGLKDSR EEQVKQESMQ GKKSSSLVDI REEETEGGSR
RLSLPGLLSQ VSPRLLRKAA RVKTRTVVLT PTYSGEADAL LPSLRTEVWT WGKGKEGQLG
HGDVLPRLQP LCVKCLDGKE VIHLEAGGYH SLALTAKSQV YSWGSNTFGQ LGHSDFPTTV
PRLAKISSEN GVWSIAAGRD YSLFLVDTED FQPGLYYSGR QDPTEGDNLP ENHSGSKTPV
LLSCSKLGYI SRVTAGKDSY LALVDKNIMG YIASLHELAT TERRFYSKLS DIKSQILRPL
LSLENLGTTT TVQLLQEVAS RFSKLCYLIG QHGASLSSFL HGVKEARSLV ILKHSSLFLD
SYTEYCTSIT NFLVMGGFQL LAKPAIDFLN KNQELLQDLS EVNDENTQLM EILNTLFFLP
IRRLHNYAKV LLKLATCFEV ASPEYQKLQD SSSCYECLAL HLGRKRKEAE YTLGFWKTFP
GKMTDSLRKP ERRLLCESSN RALSLQHAGR FSVNWFILFN DALVHAQFST HHVFPLATLW
AEPLSEEAGG VNGLKITTPE EQFTLISSTP QEKTKWLRAI SQAVDQALRG MSDLPPYGSG
SSVQRQEPPI SRSAKYTFYK DPRLKDATYD GRWLSGKPHG RGVLKWPDGK MYSGMFRNGL
EDGYGEYRIP NKAMNKEDHY VGHWKEGKMC GQGVYSYASG EVFEGCFQDN MRHGHGLLRS
GKLTSSSPSM FIGQWVMDKK AGYGVFDDIT RGEKYMGMWQ DDVCQGNGVV VTQFGLYYEG
NFHLNKMMGN GVLLSEDDTI YEGEFSDDWT LSGKGTLTMP NGDYIEGYFS GEWGSGIKIT
GTYFKPSLYE SDKDRPKVFR KLGNLAVPAD EKWKAVFDEC WRQLGCEGPG QGEVWKAWDN
IAVALTTSRR QHRDSPEILS RSQTQTLESL EFIPQHVGAF SVEKYDDIRK YLIKACDTPL
HPLGRLVETL VAVYRMTYVG VGANRRLLQE AVKEIKSYLK RIFQLVRFLF PELPEEGSTI
PLSAPLPTER KSFCTGKSDS RSESPEPGYV VTSSGLLLPV LLPRLYPPLF MLYALDNDRE
EDIYWECVLR LNKQPDIALL GFLGVQRKFW PATLSILGES KKVLPTTKDA CFASAVECLQ
QISTTFTPSD KLKVIQQTFE EISQSVLASL HEDFLWSMDD LFPVFLYVVL RARIRNLGSE
VHLIEDLMDP YLQHGEQGIM FTTLKACYYQ IQREKLN*

mutated AA sequence

MDSKKRSSTE AEGSKERGLV HIWQAGSFPI TPERLPGWGG KTVLQAALGV KHGVLLTEDG
EVYSFGTLPW RSGPVEICPS SPILENALVG QYVITVATGS FHSGAVTDNG VAYMWGENSA
GQCAVANQQY VPEPNPVSIA DSEASPLLAV RILQLAYGEE HTLALSISRE IWAWGTGCQL
GLITTAFPVT KPQKVEHLAG RVVLQVACGA FHSLALVQCL PSQDLKPVPE RCNQCSQLLI
TMTDKEDHVI ISDSHCCPLG VTLTESQAEN HASTALSPST ETLDRQEEVF ENTLVANDQS
VATELNAVSA QITSSDAMSS QQNVMGTTEI SSARNIPSYP DTQAVNEYLR KLSDHSVRED
SEHGEKPVPS QPLLEEAIPN LHSPPTTSTS ALNSLVVSCA SAVGVRVAAT YEAGALSLKK
VMNFYSTTPC ETGAQAGSSA IGPEGLKDSR EEQVKQESMQ GKKSSSLVDI REEETEGGSR
RLSLPGLLSQ VSPRLLRKAA RVKTRTVVLT PTYSGEADAL LPSLRTEVWT WGKGKEGQLG
HGDVLPRLQP LCVKCLDGKE VIHLEAGGYH SLALTAKSQV YSWGSNTFGQ LGHSDFPTTV
PRLAKISSEN GVWSIAAGRD YSLFLVDTED FQPGLYYSGR QDPTEGDNLP ENHSGSKTPV
LLSCSKLGYI SRVTAGKDSY LALVDKNIMG YIASLHELAT TERRFYSKLS DIKSQILRPL
LSLENLGTTT TVQLLQEVAS RFSKLCYLIG QHGASLSSFL HGVKEARSLV ILKHSSLFLD
SYTEYCTSIT NFLVMGGFQL LAKPAIDFLN KNQELLQDLS EVNDENTQLM EILNTLFFLP
IRRLHNYAKV LLKLATCFEV ASPEYQKLQD SSSCYECLAL HLGRKRKEAE YTLGFWKTFP
GKMTDSLRKP ERRLLCESSN RALSLQHAGR FSVNWFILFN DALVHAQFST HHVFPLATLW
AEPLSEEAGG VNGLKITTPE EQFTLISSTP QEKTKWLRAI SQAVDQALRG MSDLPPYGSG
SSVQRQEPPI SRSAKYTFYK DPRLKDATYD GRWLSGKPHG RGVLKWPDGK MYSGMFRNGL
EDGYGEYRIP NKAMNKEDHY VGHWKEGKMC GQGVYSYASG EVFEGCFQDN MRHGHGLLRS
GKLTSSSPSM FIGQWVMDKK AGYGVFDDIT RGEKYMGMWQ DDVCQGNGVV VTQFGLYYEG
NFHLNKMMGN GVLLSEDDTI YEGEFSDDWT LSGKGTLTMP NGDYIEGYFS GEWGSGIKIT
GTYFKPSLYE SDKDRPKVFR KLGNLAVPAD EKWKAVFDEC WRQLGCEGPG QGEVWKAWDN
IAVALTTSRR QHRDSPEILS RSQTQTLESL EFIPQHVGAF SVEKYDDIRK YLIKACDTPL
HPLGRLVETL VAVYRMTYVG VGANRRLLQE AVKEIKSYLK RIFQLVRFLF PELPEEGSTI
PLSAPLPTER KSFCTGKSDS RSESPEPGYV VTSSGLLLPV LLPRLYPPLF MLYALDNDRE
EDIYWECVLR LNKQPDIALL GFLGVQRKFW PATLSILGES KKVLPTTKDA CFASAVECLQ
QISTTFTPSD KLKVIQQTFE EISQSVLASL HEDFLWSMDD LFPVFLYVVL RARIRNLGSE
VHLIEDLMDP YLQHGEQGIM FTTLKACYYQ IQREKLN*

speed

0.94 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: 0.999999999986834 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM061636)
known disease mutation: rs4415 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr2:202626247C>TN/A show variant in all transcripts IGV

HGNC symbol

ALS2

Ensembl transcript ID

ENST00000467448

Genbank transcript ID

NM_001135745

UniProt peptide

Q96Q42

alteration type

single base exchange

alteration region

CDS

DNA changes

c.470G>A
cDNA.610G>A
g.19666G>A

AA changes

C157Y Score: 194 explain score(s)

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

157

frameshift

known variant

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	0.796	1
	6	1
(flanking)	4.969	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
Donor increased	19668	wt: 0.41 / mu: 0.85	wt: CGTGTGGCGAGGAGC mu: CGTATGGCGAGGAGC	TGTG\|gcga
Donor increased	19667	wt: 0.49 / mu: 0.74	wt: GCGTGTGGCGAGGAG mu: GCGTATGGCGAGGAG	GTGT\|ggcg
Donor marginally increased	19670	wt: 0.9582 / mu: 0.9810 (marginal change - not scored)	wt: TGTGGCGAGGAGCAC mu: TATGGCGAGGAGCAC	TGGC\|gagg

distance from splice site

295

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

157

mutated

not conserved

157

Ptroglodytes

all identical

ENSPTRG00000012811

157

Mmulatta

no homologue

Fcatus

all identical

ENSFCAG00000004007

157

Mmusculus

all identical

ENSMUSG00000026024

157

Ggallus

all identical

ENSGALG00000008415

157

Trubripes

all identical

ENSTRUG00000009974

150

Drerio

all identical

ENSDARG00000076924

152

Dmelanogaster

all identical

FBgn0037116

353

Celegans

no homologue

Xtropicalis

all identical

ENSXETG00000012406

155

protein features

start (aa)	end (aa)	feature	details
109	167	REPEAT	RCC1 2.	lost
169	218	REPEAT	RCC1 3.	might get lost (downstream of altered splice site)
483	483	MOD_RES	Phosphoserine.	might get lost (downstream of altered splice site)
492	492	MOD_RES	Phosphoserine.	might get lost (downstream of altered splice site)
525	576	REPEAT	RCC1 4.	might get lost (downstream of altered splice site)
533	533	MOD_RES	N6-acetyllysine.	might get lost (downstream of altered splice site)
578	627	REPEAT	RCC1 5.	might get lost (downstream of altered splice site)
690	885	DOMAIN	DH.	might get lost (downstream of altered splice site)
901	1007	DOMAIN	PH.	might get lost (downstream of altered splice site)
1049	1071	REPEAT	MORN 1.	might get lost (downstream of altered splice site)
1072	1094	REPEAT	MORN 2.	might get lost (downstream of altered splice site)
1100	1122	REPEAT	MORN 3.	might get lost (downstream of altered splice site)
1123	1145	REPEAT	MORN 4.	might get lost (downstream of altered splice site)
1151	1173	REPEAT	MORN 5.	might get lost (downstream of altered splice site)
1175	1197	REPEAT	MORN 6.	might get lost (downstream of altered splice site)
1198	1220	REPEAT	MORN 7.	might get lost (downstream of altered splice site)
1221	1244	REPEAT	MORN 8.	might get lost (downstream of altered splice site)
1344	1344	MOD_RES	Phosphothreonine.	might get lost (downstream of altered splice site)
1464	1464	MOD_RES	Phosphoserine.	might get lost (downstream of altered splice site)
1513	1657	DOMAIN	VPS9.	might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

1191 / 1191

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

397 / 397

position of stopcodon in wt / mu cDNA

1331 / 1331

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

141 / 141

chromosome

strand

-1

last intron/exon boundary

316

theoretical NMD boundary in CDS

125

length of CDS

1191

coding sequence (CDS) position

470

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

610

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

19666

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

202626247

original gDNA sequence snippet

CAGGATTTTACAGTTGGCGTGTGGCGAGGAGCACACTCTGG

altered gDNA sequence snippet

CAGGATTTTACAGTTGGCGTATGGCGAGGAGCACACTCTGG

original cDNA sequence snippet

CAGGATTTTACAGTTGGCGTGTGGCGAGGAGCACACTCTGG

altered cDNA sequence snippet

CAGGATTTTACAGTTGGCGTATGGCGAGGAGCACACTCTGG

wildtype AA sequence

mutated AA sequence

speed

0.78 s

MutationTaster - study a chromosomal position

Results

Taster files

mutation t@sting

Prediction

disease causing

mutation t@sting

Prediction

disease causing

Problems