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 2 transcript(s)...
Querying Taster for transcript #1: ENST00000264167
Querying Taster for transcript #2: ENST00000409888
MT speed 1.03 s - this script 3.02057 s

Results

genesymbol	prediction	probability	model	prediction problem	splicing	ClinVar	amino acid changes	variant type	dbSNP ID	protein length	file
AGPS	disease_causing_automatic	0.999999999999542	simple_aae		affected	0	L469P	single base exchange	rs121434413		show file
AGPS	disease_causing_automatic	1	without_aae		affected	0		single base exchange	rs121434413		show file

Taster files

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999999999999542 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM012331)
known disease mutation: rs6647 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr2:178364389T>CN/A show variant in all transcripts IGV

HGNC symbol

AGPS

Ensembl transcript ID

ENST00000264167

Genbank transcript ID

NM_003659

UniProt peptide

O00116

alteration type

single base exchange

alteration region

CDS

DNA changes

c.1406T>C
cDNA.1552T>C
g.107018T>C

AA changes

L469P Score: 98 explain score(s)

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

469

frameshift

known variant

Reference ID: rs121434413
Allele 'C' was neither found in ExAC nor 1000G.
known disease mutation: rs6647 (pathogenic for Rhizomelic chondrodysplasia punctata type 3) dbSNP NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM012331)

known disease mutation at this position, please check HGMD for details (HGMD ID CM012331)
known disease mutation at this position, please check HGMD for details (HGMD ID CM012331)

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	0.817	0.997
	4.63	1
(flanking)	-0.081	0.982

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	107019	wt: 0.2989 / mu: 0.3078 (marginal change - not scored)	wt: CTAAGTGTAGCCACATTACTGTTTGAGGGGGATCGTGAGAA mu: CTAAGTGTAGCCACATTACCGTTTGAGGGGGATCGTGAGAA	actg\|TTTG
Donor gained	107019	0.58	mu: TTACCGTTTGAGGGG	ACCG\|tttg

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

469

mutated

not conserved

469

Ptroglodytes

all identical

ENSPTRG00000012680

469

Mmulatta

all identical

ENSMMUG00000008502

470

Fcatus

no homologue

Mmusculus

all identical

ENSMUSG00000042410

482

Ggallus

all identical

ENSGALG00000009236

449

Trubripes

all identical

ENSTRUG00000017479

455

Drerio

all identical

ENSDARG00000042821

440

Dmelanogaster

all identical

FBgn0033983

421

Celegans

all conserved

Y50D7A.7

398

Xtropicalis

all identical

ENSXETG00000008462

439

protein features

start (aa)	end (aa)	feature	details
578	578	ACT_SITE	By similarity.	might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

1977 / 1977

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

659 / 659

position of stopcodon in wt / mu cDNA

2123 / 2123

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

147 / 147

chromosome

strand

last intron/exon boundary

2002

theoretical NMD boundary in CDS

1805

length of CDS

1977

coding sequence (CDS) position

1406

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

1552

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

107018

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

178364389

original gDNA sequence snippet

GCTAAGTGTAGCCACATTACTGTTTGAGGGGGATCGTGAGA

altered gDNA sequence snippet

GCTAAGTGTAGCCACATTACCGTTTGAGGGGGATCGTGAGA

original cDNA sequence snippet

GCTAAGTGTAGCCACATTACTGTTTGAGGGGGATCGTGAGA

altered cDNA sequence snippet

GCTAAGTGTAGCCACATTACCGTTTGAGGGGGATCGTGAGA

wildtype AA sequence

MAEAAAAAGG TGLGAGASYG SAADRDRDPD PDRAGRRLRV LSGHLLGRPR EALSTNECKA
RRAASAATAA PTATPAAQES GTIPKKRQEV MKWNGWGYND SKFIFNKKGQ IELTGKRYPL
SGMGLPTFKE WIQNTLGVNV EHKTTSKASL NPSDTPPSVV NEDFLHDLKE TNISYSQEAD
DRVFRAHGHC LHEIFLLREG MFERIPDIVL WPTCHDDVVK IVNLACKYNL CIIPIGGGTS
VSYGLMCPAD ETRTIISLDT SQMNRILWVD ENNLTAHVEA GITGQELERQ LKESGYCTGH
EPDSLEFSTV GGWVSTRASG MKKNIYGNIE DLVVHIKMVT PRGIIEKSCQ GPRMSTGPDI
HHFIMGSEGT LGVITEATIK IRPVPEYQKY GSVAFPNFEQ GVACLREIAK QRCAPASIRL
MDNKQFQFGH ALKPQVSSIF TSFLDGLKKF YITKFKGFDP NQLSVATLLF EGDREKVLQH
EKQVYDIAAK FGGLAAGEDN GQRGYLLTYV IAYIRDLALE YYVLGESFET SAPWDRVVDL
CRNVKERITR ECKEKGVQFA PFSTCRVTQT YDAGACIYFY FAFNYRGISD PLTVFEQTEA
AAREEILANG GSLSHHHGVG KLRKQWLKES ISDVGFGMLK SVKEYVDPNN IFGNRNLL*

mutated AA sequence

MAEAAAAAGG TGLGAGASYG SAADRDRDPD PDRAGRRLRV LSGHLLGRPR EALSTNECKA
RRAASAATAA PTATPAAQES GTIPKKRQEV MKWNGWGYND SKFIFNKKGQ IELTGKRYPL
SGMGLPTFKE WIQNTLGVNV EHKTTSKASL NPSDTPPSVV NEDFLHDLKE TNISYSQEAD
DRVFRAHGHC LHEIFLLREG MFERIPDIVL WPTCHDDVVK IVNLACKYNL CIIPIGGGTS
VSYGLMCPAD ETRTIISLDT SQMNRILWVD ENNLTAHVEA GITGQELERQ LKESGYCTGH
EPDSLEFSTV GGWVSTRASG MKKNIYGNIE DLVVHIKMVT PRGIIEKSCQ GPRMSTGPDI
HHFIMGSEGT LGVITEATIK IRPVPEYQKY GSVAFPNFEQ GVACLREIAK QRCAPASIRL
MDNKQFQFGH ALKPQVSSIF TSFLDGLKKF YITKFKGFDP NQLSVATLPF EGDREKVLQH
EKQVYDIAAK FGGLAAGEDN GQRGYLLTYV IAYIRDLALE YYVLGESFET SAPWDRVVDL
CRNVKERITR ECKEKGVQFA PFSTCRVTQT YDAGACIYFY FAFNYRGISD PLTVFEQTEA
AAREEILANG GSLSHHHGVG KLRKQWLKES ISDVGFGMLK SVKEYVDPNN IFGNRNLL*

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: without_aae, prob: 1 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

known disease mutation at this position (HGMD CM012331)
known disease mutation: rs6647 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr2:178364389T>CN/A show variant in all transcripts IGV

HGNC symbol

AGPS

Ensembl transcript ID

ENST00000409888

Genbank transcript ID

N/A

UniProt peptide

O00116

alteration type

single base exchange

alteration region

intron

DNA changes

g.107018T>C

AA changes

N/A

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

N/A

frameshift

N/A

known variant

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	0.817	0.997
	4.63	1
(flanking)	-0.081	0.982

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	107019	wt: 0.2989 / mu: 0.3078 (marginal change - not scored)	wt: CTAAGTGTAGCCACATTACTGTTTGAGGGGGATCGTGAGAA mu: CTAAGTGTAGCCACATTACCGTTTGAGGGGGATCGTGAGAA	actg\|TTTG
Donor gained	107019	0.58	mu: TTACCGTTTGAGGGG	ACCG\|tttg

distance from splice site

21668

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

N/A

protein features

start (aa)	end (aa)	feature	details
169	169	MOD_RES	N6-acetyllysine.	might get lost (downstream of altered splice site)
202	384	DOMAIN	FAD-binding PCMH-type.	might get lost (downstream of altered splice site)
347	347	MOD_RES	N6-acetyllysine.	might get lost (downstream of altered splice site)
578	578	ACT_SITE	By similarity.	might get lost (downstream of altered splice site)

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

N/A

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

N/A

position of start ATG in wt / mu cDNA

23 / 23

chromosome

strand

last intron/exon boundary

471

theoretical NMD boundary in CDS

398

length of CDS

570

coding sequence (CDS) position

N/A

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

N/A

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

107018

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

178364389

original gDNA sequence snippet

GCTAAGTGTAGCCACATTACTGTTTGAGGGGGATCGTGAGA

altered gDNA sequence snippet

GCTAAGTGTAGCCACATTACCGTTTGAGGGGGATCGTGAGA

original cDNA sequence snippet

N/A

altered cDNA sequence snippet

N/A

wildtype AA sequence

MAEAAAAAGG TGLGAGASYG SAADRDRDPD PDRAGRRLRV LSGHLLGRPR EALSTNECKA
RRAASAATAA PTATPAAQES GTIPKKRQEV MKWNGWGYND SKFIFNKKGQ IELTGKRGIS
DPLTVFEQTE AAAREEILAN GGSLSHHHGV GKLRKQWLKE SISDVGFGML KSVKEYVDPN
NIFGNRNLL*

mutated AA sequence

N/A

speed

0.13 s

MutationTaster - study a chromosomal position

Results

Taster files

mutation t@sting

Prediction

disease causing

mutation t@sting

Prediction

disease causing

Problems