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: ENST00000293780
Querying Taster for transcript #2: ENST00000381365
MT speed 0 s - this script 3.717121 s

Results

genesymbol	prediction	probability	model	prediction problem	splicing	ClinVar	amino acid changes	variant type	dbSNP ID	protein length	file
CHRNE	disease_causing	0.999999999364842	simple_aae		affected		P141L	single base exchange	rs121909512		show file
C17orf107	disease_causing	1	without_aae		affected			single base exchange	rs121909512		show file

Taster files

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999999999364842 (explain)

Summary

amino acid sequence changed
known as potential disease variant: rs18346 (probable pathogenic)
known disease mutation at this position (HGMD CM960299)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr17:4805305G>AN/A show variant in all transcripts IGV

HGNC symbol

CHRNE

Ensembl transcript ID

ENST00000293780

Genbank transcript ID

NM_000080

UniProt peptide

Q04844

alteration type

single base exchange

alteration region

CDS

DNA changes

c.422C>T
cDNA.433C>T
g.1065C>T

AA changes

P141L Score: 98 explain score(s)

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

141

frameshift

known variant

Reference ID: rs121909512

database	homozygous (A/A)	heterozygous	allele carriers
1000G	-	-	-
ExAC	0	3	3

known as potential disease variant: rs18346 (probable pathogenic for Myasthenic syndrome, congenital, 4a, slow-channel|Myasthenic syndrome, congenital, 4b, fast-channel) dbSNP NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM960299)

known disease mutation at this position, please check HGMD for details (HGMD ID CM960299)
known disease mutation at this position, please check HGMD for details (HGMD ID CM960299)

regulatory features

Promoter Associated, Regulatory Feature, Promoter like regulatory feature
H3K27me3, Histone, Histone 3 Lysine 27 Tri-Methylation
H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation
Gene Associated, Regulatory Feature, Gene associated regulatory feature
DNase1, Open Chromatin, DNase1 Hypersensitive Site

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	-1.555	0.595
	5.219	1
(flanking)	5.219	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 increased	1073	wt: 0.69 / mu: 0.84	wt: CGTGGCTGCCTCCGGCCATCTACCGCAGCGTCTGCGCAGTG mu: CGTGGCTGCCTCTGGCCATCTACCGCAGCGTCTGCGCAGTG	atct\|ACCG
Acc gained	1075	0.34	mu: TGGCTGCCTCTGGCCATCTACCGCAGCGTCTGCGCAGTGGA	ctac\|CGCA
Acc gained	1070	0.33	mu: TGACGTGGCTGCCTCTGGCCATCTACCGCAGCGTCTGCGCA	gcca\|TCTA

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

141

mutated

not conserved

141

Ptroglodytes

all identical

ENSPTRG00000008612

141

Mmulatta

all identical

ENSMMUG00000002409

141

Fcatus

no homologue

Mmusculus

all identical

ENSMUSG00000014609

141

Ggallus

no homologue

Trubripes

no homologue

Drerio

all identical

ENSDARG00000034307

146

Dmelanogaster

no homologue

Celegans

no homologue

Xtropicalis

all identical

ENSXETG00000014957

146

protein features

start (aa)	end (aa)	feature	details
21	239	TOPO_DOM	Extracellular (Potential).	lost
148	148	DISULFID	By similarity.	might get lost (downstream of altered splice site)
161	161	CARBOHYD	N-linked (GlcNAc...) (Potential).	might get lost (downstream of altered splice site)
162	162	DISULFID	By similarity.	might get lost (downstream of altered splice site)
240	264	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
265	272	TOPO_DOM	Cytoplasmic (Potential).	might get lost (downstream of altered splice site)
273	291	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
292	306	TOPO_DOM	Extracellular (Potential).	might get lost (downstream of altered splice site)
307	328	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
329	456	TOPO_DOM	Cytoplasmic (Potential).	might get lost (downstream of altered splice site)
457	480	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
481	493	TOPO_DOM	Extracellular (Potential).	might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

1482 / 1482

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

494 / 494

position of stopcodon in wt / mu cDNA

1493 / 1493

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

12 / 12

chromosome

strand

-1

last intron/exon boundary

1338

theoretical NMD boundary in CDS

1276

length of CDS

1482

coding sequence (CDS) position

422

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

433

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

1065

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

4805305

original gDNA sequence snippet

CTCCGTGACGTGGCTGCCTCCGGCCATCTACCGCAGCGTCT

altered gDNA sequence snippet

CTCCGTGACGTGGCTGCCTCTGGCCATCTACCGCAGCGTCT

original cDNA sequence snippet

CTCCGTGACGTGGCTGCCTCCGGCCATCTACCGCAGCGTCT

altered cDNA sequence snippet

CTCCGTGACGTGGCTGCCTCTGGCCATCTACCGCAGCGTCT

wildtype AA sequence

MARAPLGVLL LLGLLGRGVG KNEELRLYHH LFNNYDPGSR PVREPEDTVT ISLKVTLTNL
ISLNEKEETL TTSVWIGIDW QDYRLNYSKD DFGGIETLRV PSELVWLPEI VLENNIDGQF
GVAYDANVLV YEGGSVTWLP PAIYRSVCAV EVTYFPFDWQ NCSLIFRSQT YNAEEVEFTF
AVDNDGKTIN KIDIDTEAYT ENGEWAIDFC PGVIRRHHGG ATDGPGETDV IYSLIIRRKP
LFYVINIIVP CVLISGLVLL AYFLPAQAGG QKCTVSINVL LAQTVFLFLI AQKIPETSLS
VPLLGRFLIF VMVVATLIVM NCVIVLNVSQ RTPTTHAMSP RLRHVLLELL PRLLGSPPPP
EAPRAASPPR RASSVGLLLR AEELILKKPR SELVFEGQRH RQGTWTAAFC QSLGAAAPEV
RCCVDAVNFV AESTRDQEAT GEEVSDWVRM GNALDNICFW AALVLFSVGS SLIFLGAYFN
RVPDLPYAPC IQP*

mutated AA sequence

MARAPLGVLL LLGLLGRGVG KNEELRLYHH LFNNYDPGSR PVREPEDTVT ISLKVTLTNL
ISLNEKEETL TTSVWIGIDW QDYRLNYSKD DFGGIETLRV PSELVWLPEI VLENNIDGQF
GVAYDANVLV YEGGSVTWLP LAIYRSVCAV EVTYFPFDWQ NCSLIFRSQT YNAEEVEFTF
AVDNDGKTIN KIDIDTEAYT ENGEWAIDFC PGVIRRHHGG ATDGPGETDV IYSLIIRRKP
LFYVINIIVP CVLISGLVLL AYFLPAQAGG QKCTVSINVL LAQTVFLFLI AQKIPETSLS
VPLLGRFLIF VMVVATLIVM NCVIVLNVSQ RTPTTHAMSP RLRHVLLELL PRLLGSPPPP
EAPRAASPPR RASSVGLLLR AEELILKKPR SELVFEGQRH RQGTWTAAFC QSLGAAAPEV
RCCVDAVNFV AESTRDQEAT GEEVSDWVRM GNALDNICFW AALVLFSVGS SLIFLGAYFN
RVPDLPYAPC IQP*

speed

1.07 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: without_aae, prob: 1 (explain)

Summary

known as potential disease variant: rs18346 (probable pathogenic)
known disease mutation at this position (HGMD CM960299)
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr17:4805305G>AN/A show variant in all transcripts IGV

HGNC symbol

C17orf107

Ensembl transcript ID

ENST00000381365

Genbank transcript ID

NM_001145536

UniProt peptide

N/A

alteration type

single base exchange

alteration region

3'UTR

DNA changes

cDNA.2277G>A
g.2593G>A

AA changes

N/A

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

N/A

frameshift

N/A

known variant

Reference ID: rs121909512

database	homozygous (A/A)	heterozygous	allele carriers
1000G	-	-	-
ExAC	0	3	3

regulatory features

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	-1.555	0.595
	5.219	1
(flanking)	5.219	1

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

splice sites

splice site change occurs after stopcodon (at aa 683) splice site change occurs after stopcodon (at aa 684)

effect	gDNA position	score	detection sequence	exon-intron border
Donor increased	2595	wt: 0.29 / mu: 0.57	wt: GCCGGAGGCAGCCAC mu: GCCAGAGGCAGCCAC	CGGA\|ggca
Donor marginally increased	2590	wt: 0.5287 / mu: 0.5382 (marginal change - not scored)	wt: AGATGGCCGGAGGCA mu: AGATGGCCAGAGGCA	ATGG\|ccgg
Donor gained	2593	0.45	mu: TGGCCAGAGGCAGCC	GCCA\|gagg

distance from splice site

923

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

N/A

protein features

N/A

length of protein

N/A

AA sequence altered

N/A

position of stopcodon in wt / mu CDS

N/A

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

N/A

position of stopcodon in wt / mu cDNA

N/A

poly(A) signal

signal is predicted to be ok

conservation
nucleotide level for all changes - no scoring up to now

N/A

position of start ATG in wt / mu cDNA

228 / 228

chromosome

strand

last intron/exon boundary

504

theoretical NMD boundary in CDS

226

length of CDS

573

coding sequence (CDS) position

N/A

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

2277

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

2593

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

4805305

original gDNA sequence snippet

AGACGCTGCGGTAGATGGCCGGAGGCAGCCACGTCACGGAG

altered gDNA sequence snippet

AGACGCTGCGGTAGATGGCCAGAGGCAGCCACGTCACGGAG

original cDNA sequence snippet

AGACGCTGCGGTAGATGGCCGGAGGCAGCCACGTCACGGAG

altered cDNA sequence snippet

AGACGCTGCGGTAGATGGCCAGAGGCAGCCACGTCACGGAG

wildtype AA sequence

MKGTPSSLDT LMWIYHFHSS TEVALQPPLL SSLELSVAAA HEYLEQRFRE LKSLEPPEPK
MQGMLPAPKP TLGLVLREAT ASLVSFGTTL LEISALWLQQ EARRLDGSAG PAPDGRDPGA
ALSRVAQAAG QGVRQAGAAV GASARLLVQG AWLCLCGRGL QGSASFLRQS QQQLGLGIPG
EPVSSGHGVS *

mutated AA sequence

N/A

speed

0.59 s

MutationTaster - study a chromosomal position

Results

Taster files

mutation t@sting

Prediction

disease causing

mutation t@sting

Prediction

disease causing

Problems