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: ENST00000409155
Querying Taster for transcript #2: ENST00000277315
MT speed 0 s - this script 3.60191 s

Results

genesymbol	prediction	probability	model	prediction problem	splicing	ClinVar	amino acid changes	variant type	dbSNP ID	protein length	file
ALAD	disease_causing_automatic	0.999999999520202	simple_aae		affected	0	A274T	single base exchange	rs121912983		show file
ALAD	disease_causing_automatic	0.999999999643442	simple_aae		affected	0	A257T	single base exchange	rs121912983		show file

Taster files

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999999999520202 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM900009)
known disease mutation: rs16866 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr9:116151368C>TN/A show variant in all transcripts IGV

HGNC symbol

ALAD

Ensembl transcript ID

ENST00000409155

Genbank transcript ID

NM_000031

UniProt peptide

P13716

alteration type

single base exchange

alteration region

CDS

DNA changes

c.820G>A
cDNA.1017G>A
g.12246G>A

AA changes

A274T Score: 58 explain score(s)

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

274

frameshift

known variant

Reference ID: rs121912983
Allele 'T' was neither found in ExAC nor 1000G.
known disease mutation: rs16866 (pathogenic for Porphobilinogen synthase deficiency) dbSNP NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM900009)

known disease mutation at this position, please check HGMD for details (HGMD ID CM900009)
known disease mutation at this position, please check HGMD for details (HGMD ID CM900009)

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	5.445	1
	5.445	1
(flanking)	-0.991	0.427

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	12252	wt: 0.9286 / mu: 0.9415 (marginal change - not scored)	wt: CTGACCTCCCTCTCGCCGTGTACCACGTCTCTGGAGAGTTT mu: CTGACCTCCCTCTCACCGTGTACCACGTCTCTGGAGAGTTT	gtgt\|ACCA
Acc marginally increased	12250	wt: 0.9818 / mu: 0.9834 (marginal change - not scored)	wt: CCCTGACCTCCCTCTCGCCGTGTACCACGTCTCTGGAGAGT mu: CCCTGACCTCCCTCTCACCGTGTACCACGTCTCTGGAGAGT	ccgt\|GTAC
Acc increased	12246	wt: 0.62 / mu: 0.69	wt: AGCACCCTGACCTCCCTCTCGCCGTGTACCACGTCTCTGGA mu: AGCACCCTGACCTCCCTCTCACCGTGTACCACGTCTCTGGA	ctcg\|CCGT
Acc marginally increased	12247	wt: 0.6170 / mu: 0.6224 (marginal change - not scored)	wt: GCACCCTGACCTCCCTCTCGCCGTGTACCACGTCTCTGGAG mu: GCACCCTGACCTCCCTCTCACCGTGTACCACGTCTCTGGAG	tcgc\|CGTG
Acc marginally increased	12257	wt: 0.8338 / mu: 0.8744 (marginal change - not scored)	wt: CTCCCTCTCGCCGTGTACCACGTCTCTGGAGAGTTTGCCAT mu: CTCCCTCTCACCGTGTACCACGTCTCTGGAGAGTTTGCCAT	ccac\|GTCT
Acc marginally increased	12249	wt: 0.7534 / mu: 0.8326 (marginal change - not scored)	wt: ACCCTGACCTCCCTCTCGCCGTGTACCACGTCTCTGGAGAG mu: ACCCTGACCTCCCTCTCACCGTGTACCACGTCTCTGGAGAG	gccg\|TGTA
Acc gained	12248	0.86	mu: CACCCTGACCTCCCTCTCACCGTGTACCACGTCTCTGGAGA	cacc\|GTGT

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

274

mutated

not conserved

274

Ptroglodytes

no homologue

Mmulatta

all identical

ENSMMUG00000031965

303

Fcatus

all identical

ENSFCAG00000009244

290

Mmusculus

all identical

ENSMUSG00000028393

274

Ggallus

all identical

ENSGALG00000008869

281

Trubripes

all identical

ENSTRUG00000010590

283

Drerio

all identical

ENSDARG00000052815

276

Dmelanogaster

not conserved

FBgn0036271

270

Celegans

no homologue

Xtropicalis

all identical

ENSXETG00000023474

220

protein features

start (aa)	end (aa)	feature	details
273	277	STRAND		lost
279	279	BINDING	Substrate 2.	might get lost (downstream of altered splice site)
279	290	HELIX		might get lost (downstream of altered splice site)
296	310	HELIX		might get lost (downstream of altered splice site)
313	317	STRAND		might get lost (downstream of altered splice site)
318	318	BINDING	Substrate 2.	might get lost (downstream of altered splice site)
320	326	HELIX		might get lost (downstream of altered splice site)
327	329	TURN		might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

993 / 993

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

331 / 331

position of stopcodon in wt / mu cDNA

1190 / 1190

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

198 / 198

chromosome

strand

-1

last intron/exon boundary

1129

theoretical NMD boundary in CDS

881

length of CDS

993

coding sequence (CDS) position

820

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

1017

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

12246

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

116151368

original gDNA sequence snippet

AGCACCCTGACCTCCCTCTCGCCGTGTACCACGTCTCTGGA

altered gDNA sequence snippet

AGCACCCTGACCTCCCTCTCACCGTGTACCACGTCTCTGGA

original cDNA sequence snippet

AGCACCCTGACCTCCCTCTCGCCGTGTACCACGTCTCTGGA

altered cDNA sequence snippet

AGCACCCTGACCTCCCTCTCACCGTGTACCACGTCTCTGGA

wildtype AA sequence

MQPQSVLHSG YFHPLLRAWQ TATTTLNASN LIYPIFVTDV PDDIQPITSL PGVARYGVKR
LEEMLRPLVE EGLRCVLIFG VPSRVPKDER GSAADSEESP AIEAIHLLRK TFPNLLVACD
VCLCPYTSHG HCGLLSENGA FRAEESRQRL AEVALAYAKA GCQVVAPSDM MDGRVEAIKE
ALMAHGLGNR VSVMSYSAKF ASCFYGPFRD AAKSSPAFGD RRCYQLPPGA RGLALRAVDR
DVREGADMLM VKPGMPYLDI VREVKDKHPD LPLAVYHVSG EFAMLWHGAQ AGAFDLKAAV
LEAMTAFRRA GADIIITYYT PQLLQWLKEE *

mutated AA sequence

MQPQSVLHSG YFHPLLRAWQ TATTTLNASN LIYPIFVTDV PDDIQPITSL PGVARYGVKR
LEEMLRPLVE EGLRCVLIFG VPSRVPKDER GSAADSEESP AIEAIHLLRK TFPNLLVACD
VCLCPYTSHG HCGLLSENGA FRAEESRQRL AEVALAYAKA GCQVVAPSDM MDGRVEAIKE
ALMAHGLGNR VSVMSYSAKF ASCFYGPFRD AAKSSPAFGD RRCYQLPPGA RGLALRAVDR
DVREGADMLM VKPGMPYLDI VREVKDKHPD LPLTVYHVSG EFAMLWHGAQ AGAFDLKAAV
LEAMTAFRRA GADIIITYYT PQLLQWLKEE *

speed

0.75 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: 0.999999999643442 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM900009)
known disease mutation: rs16866 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr9:116151368C>TN/A show variant in all transcripts IGV

HGNC symbol

ALAD

Ensembl transcript ID

ENST00000277315

Genbank transcript ID

N/A

UniProt peptide

P13716

alteration type

single base exchange

alteration region

CDS

DNA changes

c.769G>A
cDNA.1031G>A
g.12246G>A

AA changes

A257T Score: 58 explain score(s)

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

257

frameshift

known variant

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	5.445	1
	5.445	1
(flanking)	-0.991	0.427

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	12252	wt: 0.9286 / mu: 0.9415 (marginal change - not scored)	wt: CTGACCTCCCTCTCGCCGTGTACCACGTCTCTGGAGAGTTT mu: CTGACCTCCCTCTCACCGTGTACCACGTCTCTGGAGAGTTT	gtgt\|ACCA
Acc marginally increased	12250	wt: 0.9818 / mu: 0.9834 (marginal change - not scored)	wt: CCCTGACCTCCCTCTCGCCGTGTACCACGTCTCTGGAGAGT mu: CCCTGACCTCCCTCTCACCGTGTACCACGTCTCTGGAGAGT	ccgt\|GTAC
Acc increased	12246	wt: 0.62 / mu: 0.69	wt: AGCACCCTGACCTCCCTCTCGCCGTGTACCACGTCTCTGGA mu: AGCACCCTGACCTCCCTCTCACCGTGTACCACGTCTCTGGA	ctcg\|CCGT
Acc marginally increased	12247	wt: 0.6170 / mu: 0.6224 (marginal change - not scored)	wt: GCACCCTGACCTCCCTCTCGCCGTGTACCACGTCTCTGGAG mu: GCACCCTGACCTCCCTCTCACCGTGTACCACGTCTCTGGAG	tcgc\|CGTG
Acc marginally increased	12257	wt: 0.8338 / mu: 0.8744 (marginal change - not scored)	wt: CTCCCTCTCGCCGTGTACCACGTCTCTGGAGAGTTTGCCAT mu: CTCCCTCTCACCGTGTACCACGTCTCTGGAGAGTTTGCCAT	ccac\|GTCT
Acc marginally increased	12249	wt: 0.7534 / mu: 0.8326 (marginal change - not scored)	wt: ACCCTGACCTCCCTCTCGCCGTGTACCACGTCTCTGGAGAG mu: ACCCTGACCTCCCTCTCACCGTGTACCACGTCTCTGGAGAG	gccg\|TGTA
Acc gained	12248	0.86	mu: CACCCTGACCTCCCTCTCACCGTGTACCACGTCTCTGGAGA	cacc\|GTGT

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

257

mutated

not conserved

257

Ptroglodytes

no homologue

Mmulatta

all identical

ENSMMUG00000031965

303

Fcatus

all identical

ENSFCAG00000009244

290

Mmusculus

all identical

ENSMUSG00000028393

274

Ggallus

all identical

ENSGALG00000008869

281

Trubripes

all identical

ENSTRUG00000010590

283

Drerio

all identical

ENSDARG00000052815

276

Dmelanogaster

not conserved

FBgn0036271

270

Celegans

no homologue

Xtropicalis

all identical

ENSXETG00000023474

220

protein features

start (aa)	end (aa)	feature	details
255	257	HELIX		lost
258	267	HELIX		might get lost (downstream of altered splice site)
273	277	STRAND		might get lost (downstream of altered splice site)
279	279	BINDING	Substrate 2.	might get lost (downstream of altered splice site)
279	290	HELIX		might get lost (downstream of altered splice site)
296	310	HELIX		might get lost (downstream of altered splice site)
313	317	STRAND		might get lost (downstream of altered splice site)
318	318	BINDING	Substrate 2.	might get lost (downstream of altered splice site)
320	326	HELIX		might get lost (downstream of altered splice site)
327	329	TURN		might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

942 / 942

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

314 / 314

position of stopcodon in wt / mu cDNA

1204 / 1204

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

263 / 263

chromosome

strand

-1

last intron/exon boundary

1143

theoretical NMD boundary in CDS

830

length of CDS

942

coding sequence (CDS) position

769

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

1031

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

12246

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

116151368

original gDNA sequence snippet

AGCACCCTGACCTCCCTCTCGCCGTGTACCACGTCTCTGGA

altered gDNA sequence snippet

AGCACCCTGACCTCCCTCTCACCGTGTACCACGTCTCTGGA

original cDNA sequence snippet

AGCACCCTGACCTCCCTCTCGCCGTGTACCACGTCTCTGGA

altered cDNA sequence snippet

AGCACCCTGACCTCCCTCTCACCGTGTACCACGTCTCTGGA

wildtype AA sequence

MQPQSVLHSG YFHPLLRAWQ TATTTLNASN LIYPIFVTYG VKRLEEMLRP LVEEGLRCVL
IFGVPSRVPK DERGSAADSE ESPAIEAIHL LRKTFPNLLV ACDVCLCPYT SHGHCGLLSE
NGAFRAEESR QRLAEVALAY AKAGCQVVAP SDMMDGRVEA IKEALMAHGL GNRVSVMSYS
AKFASCFYGP FRDAAKSSPA FGDRRCYQLP PGARGLALRA VDRDVREGAD MLMVKPGMPY
LDIVREVKDK HPDLPLAVYH VSGEFAMLWH GAQAGAFDLK AAVLEAMTAF RRAGADIIIT
YYTPQLLQWL KEE*

mutated AA sequence

MQPQSVLHSG YFHPLLRAWQ TATTTLNASN LIYPIFVTYG VKRLEEMLRP LVEEGLRCVL
IFGVPSRVPK DERGSAADSE ESPAIEAIHL LRKTFPNLLV ACDVCLCPYT SHGHCGLLSE
NGAFRAEESR QRLAEVALAY AKAGCQVVAP SDMMDGRVEA IKEALMAHGL GNRVSVMSYS
AKFASCFYGP FRDAAKSSPA FGDRRCYQLP PGARGLALRA VDRDVREGAD MLMVKPGMPY
LDIVREVKDK HPDLPLTVYH VSGEFAMLWH GAQAGAFDLK AAVLEAMTAF RRAGADIIIT
YYTPQLLQWL KEE*

speed

0.85 s

MutationTaster - study a chromosomal position

Results

Taster files

mutation t@sting

Prediction

disease causing

mutation t@sting

Prediction

disease causing

Problems