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: ENST00000242592
Querying Taster for transcript #2: ENST00000411593
MT speed 0 s - this script 4.587831 s

Results

genesymbol	prediction	probability	model	prediction problem	splicing	ClinVar	amino acid changes	variant type	dbSNP ID	protein length	file
ACADS	disease_causing_automatic	0.999999999959623	simple_aae		affected	0	S353L	single base exchange	rs28941773		show file
ACADS	disease_causing_automatic	0.999999999959623	simple_aae		affected	0	S349L	single base exchange	rs28941773		show file

Taster files

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999999999959623 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM010008)
known disease mutation: rs3836 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr12:121176971C>TN/A show variant in all transcripts IGV

HGNC symbol

ACADS

Ensembl transcript ID

ENST00000242592

Genbank transcript ID

NM_000017

UniProt peptide

P16219

alteration type

single base exchange

alteration region

CDS

DNA changes

c.1058C>T
cDNA.1209C>T
g.13434C>T

AA changes

S353L Score: 145 explain score(s)

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

353

frameshift

known variant

Reference ID: rs28941773

database	homozygous (T/T)	heterozygous	allele carriers
1000G	-	-	-
ExAC	0	14	14

known disease mutation: rs3836 (pathogenic for Deficiency of butyryl-CoA dehydrogenase|not provided) dbSNP NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM010008)

known disease mutation at this position, please check HGMD for details (HGMD ID CM010008)
known disease mutation at this position, please check HGMD for details (HGMD ID CM010008)

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	4.296	0.995
	5.191	0.995
(flanking)	-2.647	0.028

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	13438	wt: 0.51 / mu: 0.61	wt: TCGGAGGCCGCGACC mu: TTGGAGGCCGCGACC	GGAG\|gccg
Donor marginally increased	13432	wt: 0.4679 / mu: 0.5231 (marginal change - not scored)	wt: GCCGCCTCGGAGGCC mu: GCCGCCTTGGAGGCC	CGCC\|tcgg

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

353

mutated

not conserved

353

Ptroglodytes

all identical

ENSPTRG00000005547

353

Mmulatta

all identical

ENSMMUG00000020648

353

Fcatus

all identical

ENSFCAG00000002402

283

Mmusculus

all identical

ENSMUSG00000029545

353

Ggallus

all identical

ENSGALG00000007072

357

Trubripes

all identical

ENSTRUG00000018610

353

Drerio

all identical

ENSDARG00000030781

365

Dmelanogaster

all identical

FBgn0038742

346

Celegans

no homologue

Xtropicalis

all identical

ENSXETG00000012275

350

protein features

start (aa)	end (aa)	feature	details
342	367	HELIX		lost
365	369	NP_BIND	FAD; shared with dimeric partner.	might get lost (downstream of altered splice site)
368	372	HELIX		might get lost (downstream of altered splice site)
378	388	HELIX		might get lost (downstream of altered splice site)
389	392	TURN		might get lost (downstream of altered splice site)
392	392	ACT_SITE	Proton acceptor (By similarity).	might get lost (downstream of altered splice site)
393	393	BINDING	Substrate; via amide nitrogen.	might get lost (downstream of altered splice site)
394	396	NP_BIND	FAD.	might get lost (downstream of altered splice site)
395	411	HELIX		might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

1239 / 1239

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

413 / 413

position of stopcodon in wt / mu cDNA

1390 / 1390

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

152 / 152

chromosome

strand

last intron/exon boundary

1238

theoretical NMD boundary in CDS

1036

length of CDS

1239

coding sequence (CDS) position

1058

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

1209

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

13434

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

121176971

original gDNA sequence snippet

CATGGCCAAGCTGGCCGCCTCGGAGGCCGCGACCGCCATCA

altered gDNA sequence snippet

CATGGCCAAGCTGGCCGCCTTGGAGGCCGCGACCGCCATCA

original cDNA sequence snippet

CATGGCCAAGCTGGCCGCCTCGGAGGCCGCGACCGCCATCA

altered cDNA sequence snippet

CATGGCCAAGCTGGCCGCCTTGGAGGCCGCGACCGCCATCA

wildtype AA sequence

MAAALLARAS GPARRALCPR AWRQLHTIYQ SVELPETHQM LLQTCRDFAE KELFPIAAQV
DKEHLFPAAQ VKKMGGLGLL AMDVPEELGG AGLDYLAYAI AMEEISRGCA STGVIMSVNN
SLYLGPILKF GSKEQKQAWV TPFTSGDKIG CFALSEPGNG SDAGAASTTA RAEGDSWVLN
GTKAWITNAW EASAAVVFAS TDRALQNKGI SAFLVPMPTP GLTLGKKEDK LGIRGSSTAN
LIFEDCRIPK DSILGEPGMG FKIAMQTLDM GRIGIASQAL GIAQTALDCA VNYAENRMAF
GAPLTKLQVI QFKLADMALA LESARLLTWR AAMLKDNKKP FIKEAAMAKL AASEAATAIS
HQAIQILGGM GYVTEMPAER HYRDARITEI YEGTSEIQRL VIAGHLLRSY RS*

mutated AA sequence

MAAALLARAS GPARRALCPR AWRQLHTIYQ SVELPETHQM LLQTCRDFAE KELFPIAAQV
DKEHLFPAAQ VKKMGGLGLL AMDVPEELGG AGLDYLAYAI AMEEISRGCA STGVIMSVNN
SLYLGPILKF GSKEQKQAWV TPFTSGDKIG CFALSEPGNG SDAGAASTTA RAEGDSWVLN
GTKAWITNAW EASAAVVFAS TDRALQNKGI SAFLVPMPTP GLTLGKKEDK LGIRGSSTAN
LIFEDCRIPK DSILGEPGMG FKIAMQTLDM GRIGIASQAL GIAQTALDCA VNYAENRMAF
GAPLTKLQVI QFKLADMALA LESARLLTWR AAMLKDNKKP FIKEAAMAKL AALEAATAIS
HQAIQILGGM GYVTEMPAER HYRDARITEI YEGTSEIQRL VIAGHLLRSY RS*

speed

1.32 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: 0.999999999959623 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM010008)
known disease mutation: rs3836 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr12:121176971C>TN/A show variant in all transcripts IGV

HGNC symbol

ACADS

Ensembl transcript ID

ENST00000411593

Genbank transcript ID

N/A

UniProt peptide

P16219

alteration type

single base exchange

alteration region

CDS

DNA changes

c.1046C>T
cDNA.1071C>T
g.13434C>T

AA changes

S349L Score: 145 explain score(s)

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

349

frameshift

known variant

Reference ID: rs28941773

database	homozygous (T/T)	heterozygous	allele carriers
1000G	-	-	-
ExAC	0	14	14

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	4.296	0.995
	5.191	0.995
(flanking)	-2.647	0.028

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	13438	wt: 0.51 / mu: 0.61	wt: TCGGAGGCCGCGACC mu: TTGGAGGCCGCGACC	GGAG\|gccg
Donor marginally increased	13432	wt: 0.4679 / mu: 0.5231 (marginal change - not scored)	wt: GCCGCCTCGGAGGCC mu: GCCGCCTTGGAGGCC	CGCC\|tcgg

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

349

mutated

not conserved

349

Ptroglodytes

all identical

ENSPTRG00000005547

353

Mmulatta

all identical

ENSMMUG00000020648

353

Fcatus

all identical

ENSFCAG00000002402

283

Mmusculus

all identical

ENSMUSG00000029545

353

Ggallus

all identical

ENSGALG00000007072

357

Trubripes

all identical

ENSTRUG00000018610

353

Drerio

all identical

ENSDARG00000030781

365

Dmelanogaster

all identical

FBgn0038742

346

Celegans

no homologue

Xtropicalis

all identical

ENSXETG00000012275

350

protein features

start (aa)	end (aa)	feature	details
342	367	HELIX		lost
365	369	NP_BIND	FAD; shared with dimeric partner.	might get lost (downstream of altered splice site)
368	372	HELIX		might get lost (downstream of altered splice site)
378	388	HELIX		might get lost (downstream of altered splice site)
389	392	TURN		might get lost (downstream of altered splice site)
392	392	ACT_SITE	Proton acceptor (By similarity).	might get lost (downstream of altered splice site)
393	393	BINDING	Substrate; via amide nitrogen.	might get lost (downstream of altered splice site)
394	396	NP_BIND	FAD.	might get lost (downstream of altered splice site)
395	411	HELIX		might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

1227 / 1227

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

409 / 409

position of stopcodon in wt / mu cDNA

1252 / 1252

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

26 / 26

chromosome

strand

last intron/exon boundary

1100

theoretical NMD boundary in CDS

1024

length of CDS

1227

coding sequence (CDS) position

1046

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

1071

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

13434

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

121176971

original gDNA sequence snippet

CATGGCCAAGCTGGCCGCCTCGGAGGCCGCGACCGCCATCA

altered gDNA sequence snippet

CATGGCCAAGCTGGCCGCCTTGGAGGCCGCGACCGCCATCA

original cDNA sequence snippet

CATGGCCAAGCTGGCCGCCTCGGAGGCCGCGACCGCCATCA

altered cDNA sequence snippet

CATGGCCAAGCTGGCCGCCTTGGAGGCCGCGACCGCCATCA

wildtype AA sequence

MAAALLARAS GPARRALCPR AWRQLHTIYQ SVELPETHQM LLQTCRDFAE KELFPIAAQV
DKEHLFPAAQ VKKMGGLGLL AMDVPEELGG AGLDYLAYAI AMEEISRGCA STGVIMSVNN
SLYLGPILKF GSKEQKQAWV TPFTSGDKIG CFALSEPGPS LLGPTGPIFA LGQVGCPCPS
SAATEACTFP RSRQRVSRPE LLREGISAFL VPMPTPGLTL GKKEDKLGIR GSSTANLIFE
DCRIPKDSIL GEPGMGFKIA MQTLDMGRIG IASQALGIAQ TALDCAVNYA ENRMAFGAPL
TKLQVIQFKL ADMALALESA RLLTWRAAML KDNKKPFIKE AAMAKLAASE AATAISHQAI
QILGGMGYVT EMPAERHYRD ARITEIYEGT SEIQRLVIAG HLLRSYRS*

mutated AA sequence

MAAALLARAS GPARRALCPR AWRQLHTIYQ SVELPETHQM LLQTCRDFAE KELFPIAAQV
DKEHLFPAAQ VKKMGGLGLL AMDVPEELGG AGLDYLAYAI AMEEISRGCA STGVIMSVNN
SLYLGPILKF GSKEQKQAWV TPFTSGDKIG CFALSEPGPS LLGPTGPIFA LGQVGCPCPS
SAATEACTFP RSRQRVSRPE LLREGISAFL VPMPTPGLTL GKKEDKLGIR GSSTANLIFE
DCRIPKDSIL GEPGMGFKIA MQTLDMGRIG IASQALGIAQ TALDCAVNYA ENRMAFGAPL
TKLQVIQFKL ADMALALESA RLLTWRAAML KDNKKPFIKE AAMAKLAALE AATAISHQAI
QILGGMGYVT EMPAERHYRD ARITEIYEGT SEIQRLVIAG HLLRSYRS*

speed

1.31 s

MutationTaster - study a chromosomal position

Results

Taster files

mutation t@sting

Prediction

disease causing

mutation t@sting

Prediction

disease causing

Problems