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 4.268293 s

Results

genesymbol	prediction	probability	model	prediction problem	splicing	ClinVar	amino acid changes	variant type	dbSNP ID	protein length	file
ERCC2	disease_causing_automatic	0.9999999998012	simple_aae		affected	0	R605W	single base exchange	rs41556519		show file
ERCC2	disease_causing_automatic	0.999999999903323	simple_aae		affected	0	R683W	single base exchange	rs41556519		show file

Taster files

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.9999999998012 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM950365)
known disease mutation: rs16793 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr19:45855610G>AN/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.1813C>T
cDNA.1841C>T
g.18567C>T

AA changes

R605W Score: 101 explain score(s)

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

605

frameshift

known variant

Reference ID: rs41556519

database	homozygous (A/A)	heterozygous	allele carriers
1000G	-	-	-
ExAC	0	6	6

known disease mutation: rs16793 (pathogenic for Xeroderma pigmentosum, group D|Trichothiodystrophy 1, photosensitive|Cerebrooculofacioskeletal syndrome 2|Inborn genetic diseases|not provided) dbSNP NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM950365)

known disease mutation at this position, please check HGMD for details (HGMD ID CM950365)
known disease mutation at this position, please check HGMD for details (HGMD ID CM950365)

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	5.205	1
	5.205	1
(flanking)	5.205	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
Acceptor lost	18566.5	sequence motif lost	-	wt: caca\|GCGG mu: caca.GTGG
Acc increased	18572	wt: 0.53 / mu: 0.59	wt: CGCTTCTGCCCACAGCGGTTTGCCCGTGGGGACAAGCGGGG mu: CGCTTCTGCCCACAGTGGTTTGCCCGTGGGGACAAGCGGGG	gttt\|GCCC
Acc marginally increased	18569	wt: 0.7542 / mu: 0.8244 (marginal change - not scored)	wt: CTGCGCTTCTGCCCACAGCGGTTTGCCCGTGGGGACAAGCG mu: CTGCGCTTCTGCCCACAGTGGTTTGCCCGTGGGGACAAGCG	gcgg\|TTTG
Acc marginally increased	18566	wt: 0.6314 / mu: 0.6469 (marginal change - not scored)	wt: GGCCTGCGCTTCTGCCCACAGCGGTTTGCCCGTGGGGACAA mu: GGCCTGCGCTTCTGCCCACAGTGGTTTGCCCGTGGGGACAA	acag\|CGGT
Acc marginally increased	18563	wt: 0.4550 / mu: 0.5093 (marginal change - not scored)	wt: CCTGGCCTGCGCTTCTGCCCACAGCGGTTTGCCCGTGGGGA mu: CCTGGCCTGCGCTTCTGCCCACAGTGGTTTGCCCGTGGGGA	ccca\|CAGC
Acc marginally increased	18576	wt: 0.7666 / mu: 0.8444 (marginal change - not scored)	wt: TCTGCCCACAGCGGTTTGCCCGTGGGGACAAGCGGGGGAAG mu: TCTGCCCACAGTGGTTTGCCCGTGGGGACAAGCGGGGGAAG	gccc\|GTGG
Acc increased	18565	wt: 0.24 / mu: 0.47	wt: TGGCCTGCGCTTCTGCCCACAGCGGTTTGCCCGTGGGGACA mu: TGGCCTGCGCTTCTGCCCACAGTGGTTTGCCCGTGGGGACA	caca\|GCGG
Acc marginally increased	18562	wt: 0.8503 / mu: 0.8516 (marginal change - not scored)	wt: CCCTGGCCTGCGCTTCTGCCCACAGCGGTTTGCCCGTGGGG mu: CCCTGGCCTGCGCTTCTGCCCACAGTGGTTTGCCCGTGGGG	gccc\|ACAG
Acc marginally increased	18558	wt: 0.8056 / mu: 0.8165 (marginal change - not scored)	wt: CTGTCCCTGGCCTGCGCTTCTGCCCACAGCGGTTTGCCCGT mu: CTGTCCCTGGCCTGCGCTTCTGCCCACAGTGGTTTGCCCGT	ttct\|GCCC

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

605

mutated

not conserved

605

Ptroglodytes

all identical

ENSPTRG00000011149

683

Mmulatta

all identical

ENSMMUG00000014419

680

Fcatus

all identical

ENSFCAG00000002679

695

Mmusculus

all identical

ENSMUSG00000030400

683

Ggallus

no homologue

Trubripes

all identical

ENSTRUG00000007303

683

Drerio

all identical

ENSDARG00000021985

683

Dmelanogaster

all identical

FBgn0261850

683

Celegans

no alignment

Y50D7A.11

n/a

Xtropicalis

all identical

ENSXETG00000018229

682

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

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

1813

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

1841

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

18567

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

45855610

original gDNA sequence snippet

GCCTGCGCTTCTGCCCACAGCGGTTTGCCCGTGGGGACAAG

altered gDNA sequence snippet

GCCTGCGCTTCTGCCCACAGTGGTTTGCCCGTGGGGACAAG

original cDNA sequence snippet

TCATGGTCTTTGCCGACAAGCGGTTTGCCCGTGGGGACAAG

altered cDNA sequence snippet

TCATGGTCTTTGCCGACAAGTGGTTTGCCCGTGGGGACAAG

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 GTLSPLDIYP KILDFHPVTM ATFTMTLARV CLCPMIIGRG
NDQVAISSKF ETREDIAVIR NYGNLLLEMS AVVPDGIVAF FTSYQYMEST VASWYEQGIL
ENIQRNKLLF IETQDGAETS VALEKYQEAC ENGRGAILLS VARGKVSEGI DFVHHYGRAV
IMFGVPYVYT QSRILKARLE YLRDQFQIRE NDFLTFDAMR HAAQCVGRAI RGKTDYGLMV
FADKWFARGD KRGKLPRWIQ EHLTDANLNL TVDEGVQVAK YFLRQMAQPF HREDQLGLSL
LSLEQLESEE TLKRIEQIAQ QL*

speed

0.95 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: 0.999999999903323 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM950365)
known disease mutation: rs16793 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr19:45855610G>AN/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.2047C>T
cDNA.2125C>T
g.18567C>T

AA changes

R683W Score: 101 explain score(s)

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

683

frameshift

known variant

Reference ID: rs41556519

database	homozygous (A/A)	heterozygous	allele carriers
1000G	-	-	-
ExAC	0	6	6

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	5.205	1
	5.205	1
(flanking)	5.205	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
Acceptor lost	18566.5	sequence motif lost	-	wt: caca\|GCGG mu: caca.GTGG
Acc increased	18572	wt: 0.53 / mu: 0.59	wt: CGCTTCTGCCCACAGCGGTTTGCCCGTGGGGACAAGCGGGG mu: CGCTTCTGCCCACAGTGGTTTGCCCGTGGGGACAAGCGGGG	gttt\|GCCC
Acc marginally increased	18569	wt: 0.7542 / mu: 0.8244 (marginal change - not scored)	wt: CTGCGCTTCTGCCCACAGCGGTTTGCCCGTGGGGACAAGCG mu: CTGCGCTTCTGCCCACAGTGGTTTGCCCGTGGGGACAAGCG	gcgg\|TTTG
Acc marginally increased	18566	wt: 0.6314 / mu: 0.6469 (marginal change - not scored)	wt: GGCCTGCGCTTCTGCCCACAGCGGTTTGCCCGTGGGGACAA mu: GGCCTGCGCTTCTGCCCACAGTGGTTTGCCCGTGGGGACAA	acag\|CGGT
Acc marginally increased	18563	wt: 0.4550 / mu: 0.5093 (marginal change - not scored)	wt: CCTGGCCTGCGCTTCTGCCCACAGCGGTTTGCCCGTGGGGA mu: CCTGGCCTGCGCTTCTGCCCACAGTGGTTTGCCCGTGGGGA	ccca\|CAGC
Acc marginally increased	18576	wt: 0.7666 / mu: 0.8444 (marginal change - not scored)	wt: TCTGCCCACAGCGGTTTGCCCGTGGGGACAAGCGGGGGAAG mu: TCTGCCCACAGTGGTTTGCCCGTGGGGACAAGCGGGGGAAG	gccc\|GTGG
Acc increased	18565	wt: 0.24 / mu: 0.47	wt: TGGCCTGCGCTTCTGCCCACAGCGGTTTGCCCGTGGGGACA mu: TGGCCTGCGCTTCTGCCCACAGTGGTTTGCCCGTGGGGACA	caca\|GCGG
Acc marginally increased	18562	wt: 0.8503 / mu: 0.8516 (marginal change - not scored)	wt: CCCTGGCCTGCGCTTCTGCCCACAGCGGTTTGCCCGTGGGG mu: CCCTGGCCTGCGCTTCTGCCCACAGTGGTTTGCCCGTGGGG	gccc\|ACAG
Acc marginally increased	18558	wt: 0.8056 / mu: 0.8165 (marginal change - not scored)	wt: CTGTCCCTGGCCTGCGCTTCTGCCCACAGCGGTTTGCCCGT mu: CTGTCCCTGGCCTGCGCTTCTGCCCACAGTGGTTTGCCCGT	ttct\|GCCC

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

683

mutated

not conserved

683

Ptroglodytes

all identical

ENSPTRG00000011149

683

Mmulatta

all identical

ENSMMUG00000014419

680

Fcatus

all identical

ENSFCAG00000002679

695

Mmusculus

all identical

ENSMUSG00000030400

683

Ggallus

no homologue

Trubripes

all identical

ENSTRUG00000007303

683

Drerio

all identical

ENSDARG00000021985

683

Dmelanogaster

all identical

FBgn0261850

683

Celegans

no alignment

Y50D7A.11

n/a

Xtropicalis

all identical

ENSXETG00000018229

682

protein features

start (aa)	end (aa)	feature	details
682	695	MOTIF	Nuclear localization signal (Potential).	lost

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

2047

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

2125

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

18567

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

45855610

original gDNA sequence snippet

GCCTGCGCTTCTGCCCACAGCGGTTTGCCCGTGGGGACAAG

altered gDNA sequence snippet

GCCTGCGCTTCTGCCCACAGTGGTTTGCCCGTGGGGACAAG

original cDNA sequence snippet

TCATGGTCTTTGCCGACAAGCGGTTTGCCCGTGGGGACAAG

altered cDNA sequence snippet

TCATGGTCTTTGCCGACAAGTGGTTTGCCCGTGGGGACAAG

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 LSPLDIYPKI LDFHPVTMAT
FTMTLARVCL CPMIIGRGND QVAISSKFET REDIAVIRNY GNLLLEMSAV VPDGIVAFFT
SYQYMESTVA SWYEQGILEN IQRNKLLFIE TQDGAETSVA LEKYQEACEN GRGAILLSVA
RGKVSEGIDF VHHYGRAVIM FGVPYVYTQS RILKARLEYL RDQFQIREND FLTFDAMRHA
AQCVGRAIRG KTDYGLMVFA DKWFARGDKR GKLPRWIQEH LTDANLNLTV DEGVQVAKYF
LRQMAQPFHR EDQLGLSLLS LEQLESEETL KRIEQIAQQL *

speed

1.32 s

MutationTaster - study a chromosomal position

Results

Taster files

mutation t@sting

Prediction

disease causing

mutation t@sting

Prediction

disease causing

Problems