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: ENST00000391945
Querying Taster for transcript #2: ENST00000391944
MT speed 0 s - this script 4.043239 s

Results

genesymbol	prediction	probability	model	prediction problem	splicing	ClinVar	amino acid changes	variant type	dbSNP ID	protein length	file
ERCC2	disease_causing_automatic	0.999999878737533	simple_aae		affected	0	L383V	single base exchange	rs121913016		show file
ERCC2	disease_causing_automatic	0.999999906870434	simple_aae		affected	0	L461V	single base exchange	rs121913016		show file

Taster files

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999999878737533 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
heterozygous in TGP or ExAC
known disease mutation at this position (HGMD CM940373)
known disease mutation: rs16779 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr19:45860626G>CN/A show variant in all transcripts IGV

HGNC symbol

ERCC2

Ensembl transcript ID

ENST00000391944

Genbank transcript ID

N/A

UniProt peptide

P18074

alteration type

single base exchange

alteration region

CDS

DNA changes

c.1147C>G
cDNA.1175C>G
g.13551C>G

AA changes

L383V Score: 32 explain score(s)

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

383

frameshift

known variant

Reference ID: rs121913016

database	homozygous (C/C)	heterozygous	allele carriers
1000G	0	7	7
ExAC	2	158	160

known disease mutation: rs16779 (pathogenic for Xeroderma pigmentosum, group D|Trichothiodystrophy 1, photosensitive|not specified|not provided) dbSNP NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM940373)

known disease mutation at this position, please check HGMD for details (HGMD ID CM940373)
known disease mutation at this position, please check HGMD for details (HGMD ID CM940373)

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	3.9	1
	4.696	0.998
(flanking)	-3.267	0.007

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	13547	wt: 0.6189 / mu: 0.6298 (marginal change - not scored)	wt: CCTCCCACTGTCCCGCCACAGACACTGTCCCCGCTGGACAT mu: CCTCCCACTGTCCCGCCACAGACAGTGTCCCCGCTGGACAT	acag\|ACAC
Acc marginally increased	13544	wt: 0.3281 / mu: 0.3550 (marginal change - not scored)	wt: ATCCCTCCCACTGTCCCGCCACAGACACTGTCCCCGCTGGA mu: ATCCCTCCCACTGTCCCGCCACAGACAGTGTCCCCGCTGGA	gcca\|CAGA
Donor gained	13547	0.43	mu: CCACAGACAGTGTCC	ACAG\|acag
Donor gained	13550	0.48	mu: CAGACAGTGTCCCCG	GACA\|gtgt

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

383

mutated

all conserved

383

Ptroglodytes

all identical

ENSPTRG00000011149

461

Mmulatta

all identical

ENSMMUG00000014419

459

Fcatus

all identical

ENSFCAG00000002679

473

Mmusculus

all identical

ENSMUSG00000030400

461

Ggallus

no homologue

Trubripes

all identical

ENSTRUG00000007303

461

Drerio

all identical

ENSDARG00000021985

461

Dmelanogaster

all identical

FBgn0261850

461

Celegans

no alignment

Y50D7A.11

n/a

Xtropicalis

all identical

ENSXETG00000018229

462

protein features

start (aa)	end (aa)	feature	details
438	637	REGION	Mediates interaction with MMS19.	might get lost (downstream of altered splice site)
682	695	MOTIF	Nuclear localization signal (Potential).	might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

2049 / 2049

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

683 / 683

position of stopcodon in wt / mu cDNA

2077 / 2077

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

29 / 29

chromosome

strand

-1

last intron/exon boundary

1985

theoretical NMD boundary in CDS

1906

length of CDS

2049

coding sequence (CDS) position

1147

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

1175

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

13551

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

45860626

original gDNA sequence snippet

CCACTGTCCCGCCACAGACACTGTCCCCGCTGGACATCTAC

altered gDNA sequence snippet

CCACTGTCCCGCCACAGACAGTGTCCCCGCTGGACATCTAC

original cDNA sequence snippet

TCATCATCACATCTGGGACACTGTCCCCGCTGGACATCTAC

altered cDNA sequence snippet

TCATCATCACATCTGGGACAGTGTCCCCGCTGGACATCTAC

wildtype AA sequence

MKLNVDGLLV YFPYDYIYPE QFSYMRELKR TLDAKGHGVL EMPSGTGKTV SLLALIMAYQ
RAYPLEVTKL IYCSRTVPEI EKVIEELRKL LNFYEKQEGE KLPFLGLALS SRKNLCIHPE
ILHANVVVYS YHYLLDPKIA DLVSKELARK AVVVFDEAHN IDNVCIDSMS VNLTRRTLDR
CQGNLETLQK TVLRIKETDE QRLRDEYRRL VEGLREASAA RETDAHLANP VLPDEVLQEA
VPGSIRTAEH FLGFLRRLLE YVKWRLRVQH VVQESPPAFL SGLAQRVCIQ RKPLRFCAER
LRSLLHTLEI TDLADFSPLT LLANFATLVS TYAKGFTIII EPFDDRTPTI ANPILHFSCM
DASLAIKPVF ERFQSVIITS GTLSPLDIYP KILDFHPVTM ATFTMTLARV CLCPMIIGRG
NDQVAISSKF ETREDIAVIR NYGNLLLEMS AVVPDGIVAF FTSYQYMEST VASWYEQGIL
ENIQRNKLLF IETQDGAETS VALEKYQEAC ENGRGAILLS VARGKVSEGI DFVHHYGRAV
IMFGVPYVYT QSRILKARLE YLRDQFQIRE NDFLTFDAMR HAAQCVGRAI RGKTDYGLMV
FADKRFARGD KRGKLPRWIQ EHLTDANLNL TVDEGVQVAK YFLRQMAQPF HREDQLGLSL
LSLEQLESEE TLKRIEQIAQ QL*

mutated AA sequence

MKLNVDGLLV YFPYDYIYPE QFSYMRELKR TLDAKGHGVL EMPSGTGKTV SLLALIMAYQ
RAYPLEVTKL IYCSRTVPEI EKVIEELRKL LNFYEKQEGE KLPFLGLALS SRKNLCIHPE
ILHANVVVYS YHYLLDPKIA DLVSKELARK AVVVFDEAHN IDNVCIDSMS VNLTRRTLDR
CQGNLETLQK TVLRIKETDE QRLRDEYRRL VEGLREASAA RETDAHLANP VLPDEVLQEA
VPGSIRTAEH FLGFLRRLLE YVKWRLRVQH VVQESPPAFL SGLAQRVCIQ RKPLRFCAER
LRSLLHTLEI TDLADFSPLT LLANFATLVS TYAKGFTIII EPFDDRTPTI ANPILHFSCM
DASLAIKPVF ERFQSVIITS GTVSPLDIYP KILDFHPVTM ATFTMTLARV CLCPMIIGRG
NDQVAISSKF ETREDIAVIR NYGNLLLEMS AVVPDGIVAF FTSYQYMEST VASWYEQGIL
ENIQRNKLLF IETQDGAETS VALEKYQEAC ENGRGAILLS VARGKVSEGI DFVHHYGRAV
IMFGVPYVYT QSRILKARLE YLRDQFQIRE NDFLTFDAMR HAAQCVGRAI RGKTDYGLMV
FADKRFARGD KRGKLPRWIQ EHLTDANLNL TVDEGVQVAK YFLRQMAQPF HREDQLGLSL
LSLEQLESEE TLKRIEQIAQ QL*

speed

0.93 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: 0.999999906870434 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
heterozygous in TGP or ExAC
known disease mutation at this position (HGMD CM940373)
known disease mutation: rs16779 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr19:45860626G>CN/A show variant in all transcripts IGV

HGNC symbol

ERCC2

Ensembl transcript ID

ENST00000391945

Genbank transcript ID

NM_000400

UniProt peptide

P18074

alteration type

single base exchange

alteration region

CDS

DNA changes

c.1381C>G
cDNA.1459C>G
g.13551C>G

AA changes

L461V Score: 32 explain score(s)

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

461

frameshift

known variant

Reference ID: rs121913016

database	homozygous (C/C)	heterozygous	allele carriers
1000G	0	7	7
ExAC	2	158	160

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	3.9	1
	4.696	0.998
(flanking)	-3.267	0.007

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	13547	wt: 0.6189 / mu: 0.6298 (marginal change - not scored)	wt: CCTCCCACTGTCCCGCCACAGACACTGTCCCCGCTGGACAT mu: CCTCCCACTGTCCCGCCACAGACAGTGTCCCCGCTGGACAT	acag\|ACAC
Acc marginally increased	13544	wt: 0.3281 / mu: 0.3550 (marginal change - not scored)	wt: ATCCCTCCCACTGTCCCGCCACAGACACTGTCCCCGCTGGA mu: ATCCCTCCCACTGTCCCGCCACAGACAGTGTCCCCGCTGGA	gcca\|CAGA
Donor gained	13547	0.43	mu: CCACAGACAGTGTCC	ACAG\|acag
Donor gained	13550	0.48	mu: CAGACAGTGTCCCCG	GACA\|gtgt

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

461

mutated

all conserved

461

Ptroglodytes

all identical

ENSPTRG00000011149

461

Mmulatta

all identical

ENSMMUG00000014419

459

Fcatus

all identical

ENSFCAG00000002679

473

Mmusculus

all identical

ENSMUSG00000030400

461

Ggallus

no homologue

Trubripes

all identical

ENSTRUG00000007303

461

Drerio

all identical

ENSDARG00000021985

461

Dmelanogaster

all identical

FBgn0261850

461

Celegans

no alignment

Y50D7A.11

n/a

Xtropicalis

all identical

ENSXETG00000018229

462

protein features

start (aa)	end (aa)	feature	details
438	637	REGION	Mediates interaction with MMS19.	lost
682	695	MOTIF	Nuclear localization signal (Potential).	might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

2283 / 2283

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

761 / 761

position of stopcodon in wt / mu cDNA

2361 / 2361

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

79 / 79

chromosome

strand

-1

last intron/exon boundary

2269

theoretical NMD boundary in CDS

2140

length of CDS

2283

coding sequence (CDS) position

1381

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

1459

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

13551

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

45860626

original gDNA sequence snippet

CCACTGTCCCGCCACAGACACTGTCCCCGCTGGACATCTAC

altered gDNA sequence snippet

CCACTGTCCCGCCACAGACAGTGTCCCCGCTGGACATCTAC

original cDNA sequence snippet

TCATCATCACATCTGGGACACTGTCCCCGCTGGACATCTAC

altered cDNA sequence snippet

TCATCATCACATCTGGGACAGTGTCCCCGCTGGACATCTAC

wildtype AA sequence

MKLNVDGLLV YFPYDYIYPE QFSYMRELKR TLDAKGHGVL EMPSGTGKTV SLLALIMAYQ
RAYPLEVTKL IYCSRTVPEI EKVIEELRKL LNFYEKQEGE KLPFLGLALS SRKNLCIHPE
VTPLRFGKDV DGKCHSLTAS YVRAQYQHDT SLPHCRFYEE FDAHGREVPL PAGIYNLDDL
KALGRRQGWC PYFLARYSIL HANVVVYSYH YLLDPKIADL VSKELARKAV VVFDEAHNID
NVCIDSMSVN LTRRTLDRCQ GNLETLQKTV LRIKETDEQR LRDEYRRLVE GLREASAARE
TDAHLANPVL PDEVLQEAVP GSIRTAEHFL GFLRRLLEYV KWRLRVQHVV QESPPAFLSG
LAQRVCIQRK PLRFCAERLR SLLHTLEITD LADFSPLTLL ANFATLVSTY AKGFTIIIEP
FDDRTPTIAN PILHFSCMDA SLAIKPVFER FQSVIITSGT LSPLDIYPKI LDFHPVTMAT
FTMTLARVCL CPMIIGRGND QVAISSKFET REDIAVIRNY GNLLLEMSAV VPDGIVAFFT
SYQYMESTVA SWYEQGILEN IQRNKLLFIE TQDGAETSVA LEKYQEACEN GRGAILLSVA
RGKVSEGIDF VHHYGRAVIM FGVPYVYTQS RILKARLEYL RDQFQIREND FLTFDAMRHA
AQCVGRAIRG KTDYGLMVFA DKRFARGDKR GKLPRWIQEH LTDANLNLTV DEGVQVAKYF
LRQMAQPFHR EDQLGLSLLS LEQLESEETL KRIEQIAQQL *

mutated AA sequence

MKLNVDGLLV YFPYDYIYPE QFSYMRELKR TLDAKGHGVL EMPSGTGKTV SLLALIMAYQ
RAYPLEVTKL IYCSRTVPEI EKVIEELRKL LNFYEKQEGE KLPFLGLALS SRKNLCIHPE
VTPLRFGKDV DGKCHSLTAS YVRAQYQHDT SLPHCRFYEE FDAHGREVPL PAGIYNLDDL
KALGRRQGWC PYFLARYSIL HANVVVYSYH YLLDPKIADL VSKELARKAV VVFDEAHNID
NVCIDSMSVN LTRRTLDRCQ GNLETLQKTV LRIKETDEQR LRDEYRRLVE GLREASAARE
TDAHLANPVL PDEVLQEAVP GSIRTAEHFL GFLRRLLEYV KWRLRVQHVV QESPPAFLSG
LAQRVCIQRK PLRFCAERLR SLLHTLEITD LADFSPLTLL ANFATLVSTY AKGFTIIIEP
FDDRTPTIAN PILHFSCMDA SLAIKPVFER FQSVIITSGT VSPLDIYPKI LDFHPVTMAT
FTMTLARVCL CPMIIGRGND QVAISSKFET REDIAVIRNY GNLLLEMSAV VPDGIVAFFT
SYQYMESTVA SWYEQGILEN IQRNKLLFIE TQDGAETSVA LEKYQEACEN GRGAILLSVA
RGKVSEGIDF VHHYGRAVIM FGVPYVYTQS RILKARLEYL RDQFQIREND FLTFDAMRHA
AQCVGRAIRG KTDYGLMVFA DKRFARGDKR GKLPRWIQEH LTDANLNLTV DEGVQVAKYF
LRQMAQPFHR EDQLGLSLLS LEQLESEETL KRIEQIAQQL *

speed

1.11 s

MutationTaster - study a chromosomal position

Results

Taster files

mutation t@sting

Prediction

disease causing

mutation t@sting

Prediction

disease causing

Problems