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: ENST00000439986
Querying Taster for transcript #2: ENST00000398179
MT speed 0 s - this script 3.643869 s

Results

genesymbol	prediction	probability	model	prediction problem	splicing	ClinVar	amino acid changes	variant type	dbSNP ID	protein length	file
CCBE1	disease_causing_automatic	0.999999999997417	simple_aae		affected	0	C174R	single base exchange	rs121908254		show file
CCBE1	disease_causing_automatic	1	without_aae		affected	0		single base exchange	rs121908254		show file

Taster files

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999999999997417 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM098499)
known disease mutation: rs450 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr18:57134004A>GN/A show variant in all transcripts IGV

HGNC symbol

CCBE1

Ensembl transcript ID

ENST00000439986

Genbank transcript ID

NM_133459

UniProt peptide

Q6UXH8

alteration type

single base exchange

alteration region

CDS

DNA changes

c.520T>C
cDNA.558T>C
g.230609T>C

AA changes

C174R Score: 180 explain score(s)

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

174

frameshift

known variant

Reference ID: rs121908254

database	homozygous (G/G)	heterozygous	allele carriers
1000G	-	-	-
ExAC	0	1	1

known disease mutation: rs450 (pathogenic for Hennekam lymphangiectasia-lymphedema syndrome 1) dbSNP NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM098499)

known disease mutation at this position, please check HGMD for details (HGMD ID CM098499)
known disease mutation at this position, please check HGMD for details (HGMD ID CM098499)

regulatory features

H3K27me3, Histone, Histone 3 Lysine 27 Tri-Methylation
H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	3.532	1
	4.219	0.997
(flanking)	-1.673	0.267

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 marginally increased	230604	wt: 0.9986 / mu: 0.9987 (marginal change - not scored)	wt: TGGGAAGACATGTAC mu: TGGGAAGACACGTAC	GGAA\|gaca
Donor gained	230608	0.35	mu: AAGACACGTACCAGG	GACA\|cgta

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

174

mutated

not conserved

174

Ptroglodytes

all identical

ENSPTRG00000010062

174

Mmulatta

all identical

ENSMMUG00000010402

174

Fcatus

no homologue

Mmusculus

all identical

ENSMUSG00000046318

175

Ggallus

all identical

ENSGALG00000002613

105

Trubripes

all identical

ENSTRUG00000012531

131

Drerio

no homologue

Dmelanogaster

no homologue

Celegans

no homologue

Xtropicalis

all identical

ENSXETG00000021161

protein features

start (aa)	end (aa)	feature	details
134	175	DOMAIN	EGF-like; calcium-binding (Potential).	lost
174	174	DISULFID	By similarity.	lost
182	182	CARBOHYD	N-linked (GlcNAc...) (Potential).	might get lost (downstream of altered splice site)
245	290	DOMAIN	Collagen-like 1.	might get lost (downstream of altered splice site)
300	333	DOMAIN	Collagen-like 2.	might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

1221 / 1221

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

407 / 407

position of stopcodon in wt / mu cDNA

1259 / 1259

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

39 / 39

chromosome

strand

-1

last intron/exon boundary

1026

theoretical NMD boundary in CDS

937

length of CDS

1221

coding sequence (CDS) position

520

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

558

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

230609

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

57134004

original gDNA sequence snippet

GGGAAGATGATGGGAAGACATGTACCAGGGGAGACAAATAT

altered gDNA sequence snippet

GGGAAGATGATGGGAAGACACGTACCAGGGGAGACAAATAT

original cDNA sequence snippet

GGGAAGATGATGGGAAGACATGTACCAGGGGAGACAAATAT

altered cDNA sequence snippet

GGGAAGATGATGGGAAGACACGTACCAGGGGAGACAAATAT

wildtype AA sequence

MVPPPPSRGG AARGQLGRSL GPLLLLLALG HTWTYREEPE DGDREICSES KIATTKYPCL
KSSGELTTCY RKKCCKGYKF VLGQCIPEDY DVCAEAPCEQ QCTDNFGRVL CTCYPGYRYD
RERHRKREKP YCLDIDECAS SNGTLCAHIC INTLGSYRCE CREGYIREDD GKTCTRGDKY
PNDTGHEKSE NMVKAGTCCA TCKEFYQMKQ TVLQLKQKIA LLPNNAADLG KYITGDKVLA
SNTYLPGPPG LPGGQGPPGS PGPKGSPGFP GMPGPPGQPG PRGSMGPMGP SPDLSHIKQG
RRGPVGPPGA PGRDGSKGER GAPGPRGSPG PPGSFDFLLL MLADIRNDIT ELQEKVFGHR
THSSAEEFPL PQEFPSYPEA MDLGSGDDHP RRTETRDLRA PRDFYP*

mutated AA sequence

MVPPPPSRGG AARGQLGRSL GPLLLLLALG HTWTYREEPE DGDREICSES KIATTKYPCL
KSSGELTTCY RKKCCKGYKF VLGQCIPEDY DVCAEAPCEQ QCTDNFGRVL CTCYPGYRYD
RERHRKREKP YCLDIDECAS SNGTLCAHIC INTLGSYRCE CREGYIREDD GKTRTRGDKY
PNDTGHEKSE NMVKAGTCCA TCKEFYQMKQ TVLQLKQKIA LLPNNAADLG KYITGDKVLA
SNTYLPGPPG LPGGQGPPGS PGPKGSPGFP GMPGPPGQPG PRGSMGPMGP SPDLSHIKQG
RRGPVGPPGA PGRDGSKGER GAPGPRGSPG PPGSFDFLLL MLADIRNDIT ELQEKVFGHR
THSSAEEFPL PQEFPSYPEA MDLGSGDDHP RRTETRDLRA PRDFYP*

speed

0.94 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 CM098499)
known disease mutation: rs450 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr18:57134004A>GN/A show variant in all transcripts IGV

HGNC symbol

CCBE1

Ensembl transcript ID

ENST00000398179

Genbank transcript ID

N/A

UniProt peptide

Q6UXH8

alteration type

single base exchange

alteration region

5'UTR

DNA changes

cDNA.310T>C
g.230609T>C

AA changes

N/A

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

N/A

frameshift

N/A

known variant

Reference ID: rs121908254

database	homozygous (G/G)	heterozygous	allele carriers
1000G	-	-	-
ExAC	0	1	1

regulatory features

H3K27me3, Histone, Histone 3 Lysine 27 Tri-Methylation
H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	3.532	1
	4.219	0.997
(flanking)	-1.673	0.267

explain score(s) and/or inspect your position(s) in in UCSC Genome Browser

splice sites

splice site change before start ATG (at aa -50) |

effect	gDNA position	score	detection sequence	exon-intron border
Donor marginally increased	230604	wt: 0.9986 / mu: 0.9987 (marginal change - not scored)	wt: TGGGAAGACATGTAC mu: TGGGAAGACACGTAC	GGAA\|gaca
Donor gained	230608	0.35	mu: AAGACACGTACCAGG	GACA\|cgta

distance from splice site

Kozak consensus sequence altered?

conservation
protein level for non-synonymous changes

N/A

protein features

start (aa)	end (aa)	feature	details
1	34	SIGNAL	Potential.	might get lost (downstream of altered splice site)
134	175	DOMAIN	EGF-like; calcium-binding (Potential).	might get lost (downstream of altered splice site)
138	138	DISULFID	By similarity.	might get lost (downstream of altered splice site)
142	142	CARBOHYD	N-linked (GlcNAc...) (Potential).	might get lost (downstream of altered splice site)
146	146	DISULFID	By similarity.	might get lost (downstream of altered splice site)
150	150	DISULFID	By similarity.	might get lost (downstream of altered splice site)
159	159	DISULFID	By similarity.	might get lost (downstream of altered splice site)
161	161	DISULFID	By similarity.	might get lost (downstream of altered splice site)
174	174	DISULFID	By similarity.	might get lost (downstream of altered splice site)
182	182	CARBOHYD	N-linked (GlcNAc...) (Potential).	might get lost (downstream of altered splice site)
245	290	DOMAIN	Collagen-like 1.	might get lost (downstream of altered splice site)
300	333	DOMAIN	Collagen-like 2.	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

464 / 464

chromosome

strand

-1

last intron/exon boundary

638

theoretical NMD boundary in CDS

124

length of CDS

408

coding sequence (CDS) position

N/A

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

310

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

230609

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

57134004

original gDNA sequence snippet

GGGAAGATGATGGGAAGACATGTACCAGGGGAGACAAATAT

altered gDNA sequence snippet

GGGAAGATGATGGGAAGACACGTACCAGGGGAGACAAATAT

original cDNA sequence snippet

GGGAAGATGATGGGAAGACATGTACCAGGGGAGACAAATAT

altered cDNA sequence snippet

GGGAAGATGATGGGAAGACACGTACCAGGGGAGACAAATAT

wildtype AA sequence

MQLTWASISL VTRCWPQTPT FQDLLACLGA RALPGPPGAP GRDGSKGERG APGPRGSPGP
PGSFDFLLLM LADIRNDITE LQEKVFGHRT HSSAEEFPLP QEFPSYPEAM DLGSGDDHPR
RTETRDLRAP RDFYP*

mutated AA sequence

N/A

speed

0.76 s

MutationTaster - study a chromosomal position

Results

Taster files

mutation t@sting

Prediction

disease causing

mutation t@sting

Prediction

disease causing

Problems