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: ENST00000543245
Querying Taster for transcript #2: ENST00000356839
Querying Taster for transcript #3: ENST00000350303
MT speed 0 s - this script 4.023443 s

Results

genesymbol	prediction	probability	model	prediction problem	splicing	ClinVar	amino acid changes	variant type	dbSNP ID	protein length	file
ACADVL	disease_causing_automatic	0.999999996356028	simple_aae		affected	0	R636W	single base exchange	rs118204014		show file
ACADVL	disease_causing_automatic	0.999999996356028	simple_aae		affected	0	R613W	single base exchange	rs118204014		show file
ACADVL	disease_causing_automatic	0.999999996356028	simple_aae		affected	0	R591W	single base exchange	rs118204014		show file

Taster files

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999999996356028 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM950004)
known disease mutation: rs1623 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr17:7128285C>TN/A show variant in all transcripts IGV

HGNC symbol

ACADVL

Ensembl transcript ID

ENST00000543245

Genbank transcript ID

NM_001270447

UniProt peptide

P49748

alteration type

single base exchange

alteration region

CDS

DNA changes

c.1906C>T
cDNA.1927C>T
g.7842C>T

AA changes

R636W Score: 101 explain score(s)

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

636

frameshift

known variant

Reference ID: rs118204014

database	homozygous (T/T)	heterozygous	allele carriers
1000G	-	-	-
ExAC	0	10	10

known disease mutation: rs1623 (pathogenic for Very long chain acyl-CoA dehydrogenase deficiency|not provided) dbSNP NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM950004)

known disease mutation at this position, please check HGMD for details (HGMD ID CM950004)
known disease mutation at this position, please check HGMD for details (HGMD ID CM950004)

regulatory features

PolII, Polymerase, RNA Polymerase II
H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	0.653	1
	3.794	1
(flanking)	4.888	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	7842	wt: 0.4210 / mu: 0.4224 (marginal change - not scored)	wt: CCTCTCCCCAGGCTGCAGCTCGGATCCGAGAGGGCATGGCC mu: CCTCTCCCCAGGCTGCAGCTTGGATCCGAGAGGGCATGGCC	gctc\|GGAT
Acc marginally increased	7833	wt: 0.4749 / mu: 0.4976 (marginal change - not scored)	wt: CCCTCCTTCCCTCTCCCCAGGCTGCAGCTCGGATCCGAGAG mu: CCCTCCTTCCCTCTCCCCAGGCTGCAGCTTGGATCCGAGAG	cagg\|CTGC
Donor marginally increased	7845	wt: 0.2015 / mu: 0.2182 (marginal change - not scored)	wt: CTCGGATCCGAGAGG mu: CTTGGATCCGAGAGG	CGGA\|tccg
Donor increased	7838	wt: 0.24 / mu: 0.42	wt: GCTGCAGCTCGGATC mu: GCTGCAGCTTGGATC	TGCA\|gctc

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

636

mutated

not conserved

636

Ptroglodytes

all identical

ENSPTRG00000008664

635

Mmulatta

all identical

ENSMMUG00000010538

635

Fcatus

no homologue

Mmusculus

all identical

ENSMUSG00000018574

614

Ggallus

no homologue

Trubripes

all identical

ENSTRUG00000013710

617

Drerio

all identical

ENSDARG00000016687

618

Dmelanogaster

all identical

FBgn0034432

585

Celegans

not conserved

E04F6.5

571

Xtropicalis

all identical

ENSXETG00000031271

404

protein features

start (aa)	end (aa)	feature	details
627	644	HELIX		lost

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

2037 / 2037

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

679 / 679

position of stopcodon in wt / mu cDNA

2058 / 2058

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

22 / 22

chromosome

strand

last intron/exon boundary

1918

theoretical NMD boundary in CDS

1846

length of CDS

2037

coding sequence (CDS) position

1906

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

1927

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

7842

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

7128285

original gDNA sequence snippet

CCTCTCCCCAGGCTGCAGCTCGGATCCGAGAGGGCATGGCC

altered gDNA sequence snippet

CCTCTCCCCAGGCTGCAGCTTGGATCCGAGAGGGCATGGCC

original cDNA sequence snippet

GGTGTATCGAGGCTGCAGCTCGGATCCGAGAGGGCATGGCC

altered cDNA sequence snippet

GGTGTATCGAGGCTGCAGCTTGGATCCGAGAGGGCATGGCC

wildtype AA sequence

MLGGLAAAAG TRIMGKEIEA EAQRPLRQTW RPGQPPAMTA KTMSSRLTAL LGQPRPGPAR
RPYAGGAAQL ALDKSDSHPS DALTRKKPAK AESKSFAVGM FKGQLTTDQV FPYPSVLNEE
QTQFLKELVE PVSRFFEEVN DPAKNDALEM VEETTWQGLK ELGAFGLQVP SELGGVGLCN
TQYARLVEIV GMHDLGVGIT LGAHQSIGFK GILLFGTKAQ KEKYLPKLAS GETVAAFCLT
EPSSGSDAAS IRTSAVPSPC GKYYTLNGSK LWISNGGLAD IFTVFAKTPV TDPATGAVKE
KITAFVVERG FGGITHGPPE KKMGIKASNT AEVFFDGVRV PSENVLGEVG SGFKVAMHIL
NNGRFGMAAA LAGTMRGIIA KAVDHATNRT QFGEKIHNFG LIQEKLARMV MLQYVTESMA
YMVSANMDQG ATDFQIEAAI SKIFGSEAAW KVTDECIQIM GGMGFMKEPG VERVLRDLRI
FRIFEGTNDI LRLFVALQGC MDKGKELSGL GSALKNPFGN AGLLLGEAGK QLRRRAGLGS
GLSLSGLVHP ELSRSGELAV RALEQFATVV EAKLIKHKKG IVNEQFLLQR LADGAIDLYA
MVVVLSRASR SLSEGHPTAQ HEKMLCDTWC IEAAARIREG MAALQSDPWQ QELYRNFKSI
SKALVERGGV VTSNPLGF*

mutated AA sequence

speed

0.79 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: 0.999999996356028 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM950004)
known disease mutation: rs1623 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr17:7128285C>TN/A show variant in all transcripts IGV

HGNC symbol

ACADVL

Ensembl transcript ID

ENST00000356839

Genbank transcript ID

NM_000018

UniProt peptide

P49748

alteration type

single base exchange

alteration region

CDS

DNA changes

c.1837C>T
cDNA.2016C>T
g.7842C>T

AA changes

R613W Score: 101 explain score(s)

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

613

frameshift

known variant

Reference ID: rs118204014

database	homozygous (T/T)	heterozygous	allele carriers
1000G	-	-	-
ExAC	0	10	10

regulatory features

PolII, Polymerase, RNA Polymerase II
H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	0.653	1
	3.794	1
(flanking)	4.888	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	7842	wt: 0.4210 / mu: 0.4224 (marginal change - not scored)	wt: CCTCTCCCCAGGCTGCAGCTCGGATCCGAGAGGGCATGGCC mu: CCTCTCCCCAGGCTGCAGCTTGGATCCGAGAGGGCATGGCC	gctc\|GGAT
Acc marginally increased	7833	wt: 0.4749 / mu: 0.4976 (marginal change - not scored)	wt: CCCTCCTTCCCTCTCCCCAGGCTGCAGCTCGGATCCGAGAG mu: CCCTCCTTCCCTCTCCCCAGGCTGCAGCTTGGATCCGAGAG	cagg\|CTGC
Donor marginally increased	7845	wt: 0.2015 / mu: 0.2182 (marginal change - not scored)	wt: CTCGGATCCGAGAGG mu: CTTGGATCCGAGAGG	CGGA\|tccg
Donor increased	7838	wt: 0.24 / mu: 0.42	wt: GCTGCAGCTCGGATC mu: GCTGCAGCTTGGATC	TGCA\|gctc

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

613

mutated

not conserved

613

Ptroglodytes

all identical

ENSPTRG00000008664

635

Mmulatta

all identical

ENSMMUG00000010538

635

Fcatus

no homologue

Mmusculus

all identical

ENSMUSG00000018574

614

Ggallus

no homologue

Trubripes

all identical

ENSTRUG00000013710

617

Drerio

all identical

ENSDARG00000016687

618

Dmelanogaster

all identical

FBgn0034432

585

Celegans

not conserved

E04F6.5

571

Xtropicalis

all identical

ENSXETG00000031271

404

protein features

start (aa)	end (aa)	feature	details
596	622	HELIX		lost
627	644	HELIX		might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

1968 / 1968

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

656 / 656

position of stopcodon in wt / mu cDNA

2147 / 2147

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

180 / 180

chromosome

strand

last intron/exon boundary

2007

theoretical NMD boundary in CDS

1777

length of CDS

1968

coding sequence (CDS) position

1837

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

2016

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

7842

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

7128285

original gDNA sequence snippet

CCTCTCCCCAGGCTGCAGCTCGGATCCGAGAGGGCATGGCC

altered gDNA sequence snippet

CCTCTCCCCAGGCTGCAGCTTGGATCCGAGAGGGCATGGCC

original cDNA sequence snippet

GGTGTATCGAGGCTGCAGCTCGGATCCGAGAGGGCATGGCC

altered cDNA sequence snippet

GGTGTATCGAGGCTGCAGCTTGGATCCGAGAGGGCATGGCC

wildtype AA sequence

MQAARMAASL GRQLLRLGGG SSRLTALLGQ PRPGPARRPY AGGAAQLALD KSDSHPSDAL
TRKKPAKAES KSFAVGMFKG QLTTDQVFPY PSVLNEEQTQ FLKELVEPVS RFFEEVNDPA
KNDALEMVEE TTWQGLKELG AFGLQVPSEL GGVGLCNTQY ARLVEIVGMH DLGVGITLGA
HQSIGFKGIL LFGTKAQKEK YLPKLASGET VAAFCLTEPS SGSDAASIRT SAVPSPCGKY
YTLNGSKLWI SNGGLADIFT VFAKTPVTDP ATGAVKEKIT AFVVERGFGG ITHGPPEKKM
GIKASNTAEV FFDGVRVPSE NVLGEVGSGF KVAMHILNNG RFGMAAALAG TMRGIIAKAV
DHATNRTQFG EKIHNFGLIQ EKLARMVMLQ YVTESMAYMV SANMDQGATD FQIEAAISKI
FGSEAAWKVT DECIQIMGGM GFMKEPGVER VLRDLRIFRI FEGTNDILRL FVALQGCMDK
GKELSGLGSA LKNPFGNAGL LLGEAGKQLR RRAGLGSGLS LSGLVHPELS RSGELAVRAL
EQFATVVEAK LIKHKKGIVN EQFLLQRLAD GAIDLYAMVV VLSRASRSLS EGHPTAQHEK
MLCDTWCIEA AARIREGMAA LQSDPWQQEL YRNFKSISKA LVERGGVVTS NPLGF*

mutated AA sequence

speed

0.96 s

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999999996356028 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM950004)
known disease mutation: rs1623 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr17:7128285C>TN/A show variant in all transcripts IGV

HGNC symbol

ACADVL

Ensembl transcript ID

ENST00000350303

Genbank transcript ID

NM_001033859

UniProt peptide

P49748

alteration type

single base exchange

alteration region

CDS

DNA changes

c.1771C>T
cDNA.1893C>T
g.7842C>T

AA changes

R591W Score: 101 explain score(s)

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

591

frameshift

known variant

Reference ID: rs118204014

database	homozygous (T/T)	heterozygous	allele carriers
1000G	-	-	-
ExAC	0	10	10

regulatory features

PolII, Polymerase, RNA Polymerase II
H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	0.653	1
	3.794	1
(flanking)	4.888	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	7842	wt: 0.4210 / mu: 0.4224 (marginal change - not scored)	wt: CCTCTCCCCAGGCTGCAGCTCGGATCCGAGAGGGCATGGCC mu: CCTCTCCCCAGGCTGCAGCTTGGATCCGAGAGGGCATGGCC	gctc\|GGAT
Acc marginally increased	7833	wt: 0.4749 / mu: 0.4976 (marginal change - not scored)	wt: CCCTCCTTCCCTCTCCCCAGGCTGCAGCTCGGATCCGAGAG mu: CCCTCCTTCCCTCTCCCCAGGCTGCAGCTTGGATCCGAGAG	cagg\|CTGC
Donor marginally increased	7845	wt: 0.2015 / mu: 0.2182 (marginal change - not scored)	wt: CTCGGATCCGAGAGG mu: CTTGGATCCGAGAGG	CGGA\|tccg
Donor increased	7838	wt: 0.24 / mu: 0.42	wt: GCTGCAGCTCGGATC mu: GCTGCAGCTTGGATC	TGCA\|gctc

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

591

mutated

not conserved

591

Ptroglodytes

all identical

ENSPTRG00000008664

635

Mmulatta

all identical

ENSMMUG00000010538

635

Fcatus

no homologue

Mmusculus

all identical

ENSMUSG00000018574

614

Ggallus

no homologue

Trubripes

all identical

ENSTRUG00000013710

617

Drerio

all identical

ENSDARG00000016687

618

Dmelanogaster

all identical

FBgn0034432

585

Celegans

not conserved

E04F6.5

571

Xtropicalis

all identical

ENSXETG00000031271

404

protein features

start (aa)	end (aa)	feature	details
562	591	HELIX		lost
596	622	HELIX		might get lost (downstream of altered splice site)
627	644	HELIX		might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

1902 / 1902

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

634 / 634

position of stopcodon in wt / mu cDNA

2024 / 2024

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

123 / 123

chromosome

strand

last intron/exon boundary

1884

theoretical NMD boundary in CDS

1711

length of CDS

1902

coding sequence (CDS) position

1771

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

1893

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

7842

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

7128285

original gDNA sequence snippet

CCTCTCCCCAGGCTGCAGCTCGGATCCGAGAGGGCATGGCC

altered gDNA sequence snippet

CCTCTCCCCAGGCTGCAGCTTGGATCCGAGAGGGCATGGCC

original cDNA sequence snippet

GGTGTATCGAGGCTGCAGCTCGGATCCGAGAGGGCATGGCC

altered cDNA sequence snippet

GGTGTATCGAGGCTGCAGCTTGGATCCGAGAGGGCATGGCC

wildtype AA sequence

MQAARMAASL GRQLLRLGGG SSRLTALLGQ PRPGPARRPY AGGAAQESKS FAVGMFKGQL
TTDQVFPYPS VLNEEQTQFL KELVEPVSRF FEEVNDPAKN DALEMVEETT WQGLKELGAF
GLQVPSELGG VGLCNTQYAR LVEIVGMHDL GVGITLGAHQ SIGFKGILLF GTKAQKEKYL
PKLASGETVA AFCLTEPSSG SDAASIRTSA VPSPCGKYYT LNGSKLWISN GGLADIFTVF
AKTPVTDPAT GAVKEKITAF VVERGFGGIT HGPPEKKMGI KASNTAEVFF DGVRVPSENV
LGEVGSGFKV AMHILNNGRF GMAAALAGTM RGIIAKAVDH ATNRTQFGEK IHNFGLIQEK
LARMVMLQYV TESMAYMVSA NMDQGATDFQ IEAAISKIFG SEAAWKVTDE CIQIMGGMGF
MKEPGVERVL RDLRIFRIFE GTNDILRLFV ALQGCMDKGK ELSGLGSALK NPFGNAGLLL
GEAGKQLRRR AGLGSGLSLS GLVHPELSRS GELAVRALEQ FATVVEAKLI KHKKGIVNEQ
FLLQRLADGA IDLYAMVVVL SRASRSLSEG HPTAQHEKML CDTWCIEAAA RIREGMAALQ
SDPWQQELYR NFKSISKALV ERGGVVTSNP LGF*

mutated AA sequence

speed

1.00 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