MutationTaster - study a chromosomal position

NEVER press reload or F5 - unless you want to start from the very beginning.
input seems to be ok - now mapping the variant to the different transcripts...
found 4 transcript(s)...
Querying Taster for transcript #1: ENST00000222214
Querying Taster for transcript #2: ENST00000591470
Querying Taster for transcript #3: ENST00000457854
Querying Taster for transcript #4: ENST00000422947
MT speed 0 s - this script 4.935631 s

Results

genesymbol	prediction	probability	model	prediction problem	splicing	ClinVar	amino acid changes	variant type	dbSNP ID	protein length	file
GCDH	disease_causing_automatic	0.999999999946452	simple_aae		affected	0	R402W	single base exchange	rs121434369		show file
GCDH	disease_causing_automatic	0.999999999946452	simple_aae		affected	0	R402W	single base exchange	rs121434369		show file
GCDH	disease_causing_automatic	0.999999999946452	simple_aae		affected	0	R402W	single base exchange	rs121434369		show file
GCDH	disease_causing_automatic	0.999999999946452	simple_aae		affected	0	R358W	single base exchange	rs121434369		show file

Taster files

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999999999946452 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM960719)
known disease mutation: rs2085 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr19:13008638C>TN/A show variant in all transcripts IGV

HGNC symbol

GCDH

Ensembl transcript ID

ENST00000222214

Genbank transcript ID

NM_000159

UniProt peptide

Q92947

alteration type

single base exchange

alteration region

CDS

DNA changes

c.1204C>T
cDNA.1415C>T
g.6799C>T

AA changes

R402W Score: 101 explain score(s)

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

402

frameshift

known variant

Reference ID: rs121434369

database	homozygous (T/T)	heterozygous	allele carriers
1000G	-	-	-
ExAC	0	27	27

known disease mutation: rs2085 (pathogenic for Glutaric aciduria, type 1|not provided) dbSNP NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM960719)

known disease mutation at this position, please check HGMD for details (HGMD ID CM960719)
known disease mutation at this position, please check HGMD for details (HGMD ID CM960719)

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	2.207	1
	3.798	1
(flanking)	5.669	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
Donor increased	6792	wt: 0.25 / mu: 0.56	wt: TATCACGTGATCCGG mu: TATCACGTGATCTGG	TCAC\|gtga
Donor marginally increased	6804	wt: 0.9900 / mu: 0.9929 (marginal change - not scored)	wt: CGGCACGCCATGAAC mu: TGGCACGCCATGAAC	GCAC\|gcca

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

402

mutated

not conserved

402

Ptroglodytes

all identical

ENSPTRG00000010548

402

Mmulatta

all identical

ENSMMUG00000007043

402

Fcatus

all identical

ENSFCAG00000000477

402

Mmusculus

all identical

ENSMUSG00000003809

402

Ggallus

no homologue

Trubripes

all identical

ENSTRUG00000008257

405

Drerio

all identical

ENSDARG00000038361

372

Dmelanogaster

all identical

FBgn0031824

385

Celegans

all identical

F54D5.7

376

Xtropicalis

all identical

ENSXETG00000007932

404

protein features

start (aa)	end (aa)	feature	details
400	410	HELIX		lost
413	415	STRAND		might get lost (downstream of altered splice site)
414	414	ACT_SITE	Proton acceptor (Probable).	might get lost (downstream of altered splice site)
414	414	MUTAGEN	E->D: Reduced catalytic activity.	might get lost (downstream of altered splice site)
415	415	BINDING	Substrate; via amide nitrogen.	might get lost (downstream of altered splice site)
416	418	NP_BIND	FAD.	might get lost (downstream of altered splice site)
417	429	HELIX		might get lost (downstream of altered splice site)
434	434	BINDING	FAD; via carbonyl oxygen.	might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

1317 / 1317

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

439 / 439

position of stopcodon in wt / mu cDNA

1528 / 1528

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

212 / 212

chromosome

strand

last intron/exon boundary

1455

theoretical NMD boundary in CDS

1193

length of CDS

1317

coding sequence (CDS) position

1204

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

1415

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

6799

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

13008638

original gDNA sequence snippet

CTGACGAGTATCACGTGATCCGGCACGCCATGAACCTGGAG

altered gDNA sequence snippet

CTGACGAGTATCACGTGATCTGGCACGCCATGAACCTGGAG

original cDNA sequence snippet

CTGACGAGTATCACGTGATCCGGCACGCCATGAACCTGGAG

altered cDNA sequence snippet

CTGACGAGTATCACGTGATCTGGCACGCCATGAACCTGGAG

wildtype AA sequence

MALRGVSVRL LSRGPGLHVL RTWVSSAAQT EKGGRTQSQL AKSSRPEFDW QDPLVLEEQL
TTDEILIRDT FRTYCQERLM PRILLANRNE VFHREIISEM GELGVLGPTI KGYGCAGVSS
VAYGLLAREL ERVDSGYRSA MSVQSSLVMH PIYAYGSEEQ RQKYLPQLAK GELLGCFGLT
EPNSGSDPSS METRAHYNSS NKSYTLNGTK TWITNSPMAD LFVVWARCED GCIRGFLLEK
GMRGLSAPRI QGKFSLRASA TGMIIMDGVE VPEENVLPGA SSLGGPFGCL NNARYGIAWG
VLGASEFCLH TARQYALDRM QFGVPLARNQ LIQKKLADML TEITLGLHAC LQLGRLKDQD
KAAPEMVSLL KRNNCGKALD IARQARDMLG GNGISDEYHV IRHAMNLEAV NTYEGTHDIH
ALILGRAITG IQAFTASK*

mutated AA sequence

speed

0.90 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: 0.999999999946452 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM960719)
known disease mutation: rs2085 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr19:13008638C>TN/A show variant in all transcripts IGV

HGNC symbol

GCDH

Ensembl transcript ID

ENST00000591470

Genbank transcript ID

N/A

UniProt peptide

Q92947

alteration type

single base exchange

alteration region

CDS

DNA changes

c.1204C>T
cDNA.1349C>T
g.6799C>T

AA changes

R402W Score: 101 explain score(s)

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

402

frameshift

known variant

Reference ID: rs121434369

database	homozygous (T/T)	heterozygous	allele carriers
1000G	-	-	-
ExAC	0	27	27

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	2.207	1
	3.798	1
(flanking)	5.669	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
Donor increased	6792	wt: 0.25 / mu: 0.56	wt: TATCACGTGATCCGG mu: TATCACGTGATCTGG	TCAC\|gtga
Donor marginally increased	6804	wt: 0.9900 / mu: 0.9929 (marginal change - not scored)	wt: CGGCACGCCATGAAC mu: TGGCACGCCATGAAC	GCAC\|gcca

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

402

mutated

not conserved

402

Ptroglodytes

all identical

ENSPTRG00000010548

402

Mmulatta

all identical

ENSMMUG00000007043

402

Fcatus

all identical

ENSFCAG00000000477

402

Mmusculus

all identical

ENSMUSG00000003809

402

Ggallus

no homologue

Trubripes

all identical

ENSTRUG00000008257

405

Drerio

all identical

ENSDARG00000038361

372

Dmelanogaster

all identical

FBgn0031824

385

Celegans

all identical

F54D5.7

376

Xtropicalis

all identical

ENSXETG00000007932

404

protein features

start (aa)	end (aa)	feature	details
400	410	HELIX		lost
413	415	STRAND		might get lost (downstream of altered splice site)
414	414	ACT_SITE	Proton acceptor (Probable).	might get lost (downstream of altered splice site)
414	414	MUTAGEN	E->D: Reduced catalytic activity.	might get lost (downstream of altered splice site)
415	415	BINDING	Substrate; via amide nitrogen.	might get lost (downstream of altered splice site)
416	418	NP_BIND	FAD.	might get lost (downstream of altered splice site)
417	429	HELIX		might get lost (downstream of altered splice site)
434	434	BINDING	FAD; via carbonyl oxygen.	might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

1317 / 1317

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

439 / 439

position of stopcodon in wt / mu cDNA

1462 / 1462

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

146 / 146

chromosome

strand

last intron/exon boundary

1389

theoretical NMD boundary in CDS

1193

length of CDS

1317

coding sequence (CDS) position

1204

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

1349

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

6799

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

13008638

original gDNA sequence snippet

CTGACGAGTATCACGTGATCCGGCACGCCATGAACCTGGAG

altered gDNA sequence snippet

CTGACGAGTATCACGTGATCTGGCACGCCATGAACCTGGAG

original cDNA sequence snippet

CTGACGAGTATCACGTGATCCGGCACGCCATGAACCTGGAG

altered cDNA sequence snippet

CTGACGAGTATCACGTGATCTGGCACGCCATGAACCTGGAG

wildtype AA sequence

mutated AA sequence

speed

0.88 s

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999999999946452 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM960719)
known disease mutation: rs2085 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr19:13008638C>TN/A show variant in all transcripts IGV

HGNC symbol

GCDH

Ensembl transcript ID

ENST00000457854

Genbank transcript ID

NM_013976

UniProt peptide

Q92947

alteration type

single base exchange

alteration region

CDS

DNA changes

c.1204C>T
cDNA.1281C>T
g.6799C>T

AA changes

R402W Score: 101 explain score(s)

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

402

frameshift

known variant

Reference ID: rs121434369

database	homozygous (T/T)	heterozygous	allele carriers
1000G	-	-	-
ExAC	0	27	27

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	2.207	1
	3.798	1
(flanking)	5.669	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
Donor increased	6792	wt: 0.25 / mu: 0.56	wt: TATCACGTGATCCGG mu: TATCACGTGATCTGG	TCAC\|gtga
Donor marginally increased	6804	wt: 0.9900 / mu: 0.9929 (marginal change - not scored)	wt: CGGCACGCCATGAAC mu: TGGCACGCCATGAAC	GCAC\|gcca

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

402

mutated

not conserved

402

Ptroglodytes

all identical

ENSPTRG00000010548

402

Mmulatta

all identical

ENSMMUG00000007043

402

Fcatus

all identical

ENSFCAG00000000477

402

Mmusculus

all identical

ENSMUSG00000003809

402

Ggallus

no homologue

Trubripes

all identical

ENSTRUG00000008257

405

Drerio

all identical

ENSDARG00000038361

372

Dmelanogaster

all identical

FBgn0031824

385

Celegans

all identical

F54D5.7

376

Xtropicalis

all identical

ENSXETG00000007932

404

protein features

start (aa)	end (aa)	feature	details
400	410	HELIX		lost
413	415	STRAND		might get lost (downstream of altered splice site)
414	414	ACT_SITE	Proton acceptor (Probable).	might get lost (downstream of altered splice site)
414	414	MUTAGEN	E->D: Reduced catalytic activity.	might get lost (downstream of altered splice site)
415	415	BINDING	Substrate; via amide nitrogen.	might get lost (downstream of altered splice site)
416	418	NP_BIND	FAD.	might get lost (downstream of altered splice site)
417	429	HELIX		might get lost (downstream of altered splice site)
434	434	BINDING	FAD; via carbonyl oxygen.	might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

1287 / 1287

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

429 / 429

position of stopcodon in wt / mu cDNA

1364 / 1364

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

78 / 78

chromosome

strand

last intron/exon boundary

1321

theoretical NMD boundary in CDS

1193

length of CDS

1287

coding sequence (CDS) position

1204

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

1281

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

6799

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

13008638

original gDNA sequence snippet

CTGACGAGTATCACGTGATCCGGCACGCCATGAACCTGGAG

altered gDNA sequence snippet

CTGACGAGTATCACGTGATCTGGCACGCCATGAACCTGGAG

original cDNA sequence snippet

CTGACGAGTATCACGTGATCCGGCACGCCATGAACCTGGAG

altered cDNA sequence snippet

CTGACGAGTATCACGTGATCTGGCACGCCATGAACCTGGAG

wildtype AA sequence

mutated AA sequence

speed

0.80 s

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999999999946452 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM960719)
known disease mutation: rs2085 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr19:13008638C>TN/A show variant in all transcripts IGV

HGNC symbol

GCDH

Ensembl transcript ID

ENST00000422947

Genbank transcript ID

N/A

UniProt peptide

Q92947

alteration type

single base exchange

alteration region

CDS

DNA changes

c.1072C>T
cDNA.1330C>T
g.6799C>T

AA changes

R358W Score: 101 explain score(s)

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

358

frameshift

known variant

Reference ID: rs121434369

database	homozygous (T/T)	heterozygous	allele carriers
1000G	-	-	-
ExAC	0	27	27

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	2.207	1
	3.798	1
(flanking)	5.669	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
Donor increased	6792	wt: 0.25 / mu: 0.56	wt: TATCACGTGATCCGG mu: TATCACGTGATCTGG	TCAC\|gtga
Donor marginally increased	6804	wt: 0.9900 / mu: 0.9929 (marginal change - not scored)	wt: CGGCACGCCATGAAC mu: TGGCACGCCATGAAC	GCAC\|gcca

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

358

mutated

not conserved

358

Ptroglodytes

all identical

ENSPTRG00000010548

402

Mmulatta

all identical

ENSMMUG00000007043

402

Fcatus

all identical

ENSFCAG00000000477

402

Mmusculus

all identical

ENSMUSG00000003809

402

Ggallus

no homologue

Trubripes

all identical

ENSTRUG00000008257

405

Drerio

all identical

ENSDARG00000038361

372

Dmelanogaster

all identical

FBgn0031824

385

Celegans

all identical

F54D5.7

376

Xtropicalis

all identical

ENSXETG00000007932

404

protein features

start (aa)	end (aa)	feature	details
330	358	HELIX		lost
364	388	HELIX		might get lost (downstream of altered splice site)
387	391	NP_BIND	FAD (By similarity).	might get lost (downstream of altered splice site)
389	394	HELIX		might get lost (downstream of altered splice site)
396	398	HELIX		might get lost (downstream of altered splice site)
400	410	HELIX		might get lost (downstream of altered splice site)
413	415	STRAND		might get lost (downstream of altered splice site)
414	414	MUTAGEN	E->D: Reduced catalytic activity.	might get lost (downstream of altered splice site)
414	414	ACT_SITE	Proton acceptor (Probable).	might get lost (downstream of altered splice site)
415	415	BINDING	Substrate; via amide nitrogen.	might get lost (downstream of altered splice site)
416	418	NP_BIND	FAD.	might get lost (downstream of altered splice site)
417	429	HELIX		might get lost (downstream of altered splice site)
434	434	BINDING	FAD; via carbonyl oxygen.	might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

1185 / 1185

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

395 / 395

position of stopcodon in wt / mu cDNA

1443 / 1443

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

259 / 259

chromosome

strand

last intron/exon boundary

1370

theoretical NMD boundary in CDS

1061

length of CDS

1185

coding sequence (CDS) position

1072

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

1330

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

6799

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

13008638

original gDNA sequence snippet

CTGACGAGTATCACGTGATCCGGCACGCCATGAACCTGGAG

altered gDNA sequence snippet

CTGACGAGTATCACGTGATCTGGCACGCCATGAACCTGGAG

original cDNA sequence snippet

CTGACGAGTATCACGTGATCCGGCACGCCATGAACCTGGAG

altered cDNA sequence snippet

CTGACGAGTATCACGTGATCTGGCACGCCATGAACCTGGAG

wildtype AA sequence

MRSSSGTPSA PTARRDSCLA SCWPIATKSL ALLPRLECSG TILAHCKFCL PGSSDSPAST
PLVAGITGYG CAGVSSVAYG LLARELERVD SGYRSAMSVQ SSLVMHPIYA YGSEEQRQKY
LPQLAKGELL GCFGLTEPNS GSDPSSMETR AHYNSSNKSY TLNGTKTWIT NSPMADLFVV
WARCEDGCIR GFLLEKGMRG LSAPRIQGKF SLRASATGMI IMDGVEVPEE NVLPGASSLG
GPFGCLNNAR YGIAWGVLGA SEFCLHTARQ YALDRMQFGV PLARNQLIQK KLADMLTEIT
LGLHACLQLG RLKDQDKAAP EMVSLLKRNN CGKALDIARQ ARDMLGGNGI SDEYHVIRHA
MNLEAVNTYE GTHDIHALIL GRAITGIQAF TASK*

mutated AA sequence

speed

1.13 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

mutation t@sting

Prediction

disease causing

Problems