MutationTaster - study a chromosomal position

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input seems to be ok - now mapping the variant to the different transcripts...
found 3 transcript(s)...
Querying Taster for transcript #1: ENST00000258530
Querying Taster for transcript #2: ENST00000539978
Querying Taster for transcript #3: ENST00000551662
MT speed 0 s - this script 4.36742 s

Results

genesymbol	prediction	probability	model	prediction problem	splicing	ClinVar	amino acid changes	variant type	dbSNP ID	protein length	file
APPL2	polymorphism_automatic	1.33816302483325e-09	simple_aae		affected		A433V	single base exchange	rs2272495		show file
APPL2	polymorphism_automatic	1.33816302483325e-09	simple_aae		affected		A439V	single base exchange	rs2272495		show file
APPL2	polymorphism_automatic	1.74240000205828e-09	simple_aae		affected		A390V	single base exchange	rs2272495		show file

Taster files

mutation t@sting

documentation

Prediction

polymorphism

Model: simple_aae, prob: 0.999999998661837 (classification due to TGP/ExAC, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
homozygous in TGP or ExAC
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr12:105583877G>AN/A show variant in all transcripts IGV

HGNC symbol

APPL2

Ensembl transcript ID

ENST00000258530

Genbank transcript ID

NM_001251904

UniProt peptide

Q8NEU8

alteration type

single base exchange

alteration region

CDS

DNA changes

c.1298C>T
cDNA.1524C>T
g.46140C>T

AA changes

A433V Score: 64 explain score(s)

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

433

frameshift

known variant

Reference ID: rs2272495

database	homozygous (A/A)	heterozygous	allele carriers
1000G	107	724	831
ExAC	2605	19402	22007

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	0.186	0
	1.488	0.003
(flanking)	0.43	0.001

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	46133	wt: 0.81 / mu: 0.93	wt: TTGTTCCCAAAGCAA mu: TTGTTCCCAAAGTAA	GTTC\|ccaa
Donor increased	46143	wt: 0.24 / mu: 0.33	wt: AGCAACAGCCAGTCT mu: AGTAACAGCCAGTCT	CAAC\|agcc

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

433

mutated

not conserved

433

Ptroglodytes

all identical

ENSPTRG00000005384

433

Mmulatta

all identical

ENSMMUG00000009524

420

Fcatus

all identical

ENSFCAG00000001461

428

Mmusculus

all identical

ENSMUSG00000020263

433

Ggallus

not conserved

ENSGALG00000012665

431

Trubripes

not conserved

ENSTRUG00000016642

432

Drerio

all conserved

ENSDARG00000078139

432

Dmelanogaster

no homologue

Celegans

no homologue

Xtropicalis

not conserved

ENSXETG00000001888

433

protein features

start (aa)	end (aa)	feature	details
448	448	CONFLICT	T -> A (in Ref. 2).	might get lost (downstream of altered splice site)
488	637	DOMAIN	PID.	might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

1995 / 1995

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

665 / 665

position of stopcodon in wt / mu cDNA

2221 / 2221

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

227 / 227

chromosome

strand

-1

last intron/exon boundary

2087

theoretical NMD boundary in CDS

1810

length of CDS

1995

coding sequence (CDS) position

1298

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

1524

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

46140

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

105583877

original gDNA sequence snippet

TGACAAGATTGTTCCCAAAGCAACAGCCAGTCTACCTGAAG

altered gDNA sequence snippet

TGACAAGATTGTTCCCAAAGTAACAGCCAGTCTACCTGAAG

original cDNA sequence snippet

TGACAAGATTGTTCCCAAAGCAACAGCCAGTCTACCTGAAG

altered cDNA sequence snippet

TGACAAGATTGTTCCCAAAGTAACAGCCAGTCTACCTGAAG

wildtype AA sequence

MPAVDKLLLE EALQDSPQTR SLLSVFEEDA GTLTDYTNQL LQAMQRVYGA QNEMCLATQQ
LSKQLLAYEK QNFALGKGDE EVISTLHYFS KVVDELNLLH TELAKQLADT MVLPIIQFRE
KDLTEVSTLK DLFGLASNEH DLSMAKYSRL PKKKENEKVK TEVGKEVAAA RRKQHLSSLQ
YYCALNALQY RKQMAMMEPM IGFAHGQINF FKKGAEMFSK RMDSFLSSVA DMVQSIQVEL
EAEAEKMRVS QQELLSVDES VYTPDSDVAA PQINRNLIQK AGYLNLRNKT GLVTTTWERL
YFFTQGGNLM CQPRGAVAGG LIQDLDNCSV MAVDCEDRRY CFQITTPNGK SGIILQAESR
KENEEWICAI NNISRQIYLT DNPEAVAIKL NQTALQAVTP ITSFGKKQES SCPSQNLKNS
EMENENDKIV PKATASLPEA EELIAPGTPI QFDIVLPATE FLDQNRGSRR TNPFGETEDE
SFPEAEDSLL QQMFIVRFLG SMAVKTDSTT EVIYEAMRQV LAARAIHNIF RMTESHLMVT
SQSLRLIDPQ TQVSRANFEL TSVTQFAAHQ ENKRLVGFVI RVPESTGEES LSTYIFESNS
EGEKICYAIN LGKEIIEVQK DPEALAQLML SIPLTNDGKY VLLNDQPDDD DGNPNEHRGA
ESEA*

mutated AA sequence

MPAVDKLLLE EALQDSPQTR SLLSVFEEDA GTLTDYTNQL LQAMQRVYGA QNEMCLATQQ
LSKQLLAYEK QNFALGKGDE EVISTLHYFS KVVDELNLLH TELAKQLADT MVLPIIQFRE
KDLTEVSTLK DLFGLASNEH DLSMAKYSRL PKKKENEKVK TEVGKEVAAA RRKQHLSSLQ
YYCALNALQY RKQMAMMEPM IGFAHGQINF FKKGAEMFSK RMDSFLSSVA DMVQSIQVEL
EAEAEKMRVS QQELLSVDES VYTPDSDVAA PQINRNLIQK AGYLNLRNKT GLVTTTWERL
YFFTQGGNLM CQPRGAVAGG LIQDLDNCSV MAVDCEDRRY CFQITTPNGK SGIILQAESR
KENEEWICAI NNISRQIYLT DNPEAVAIKL NQTALQAVTP ITSFGKKQES SCPSQNLKNS
EMENENDKIV PKVTASLPEA EELIAPGTPI QFDIVLPATE FLDQNRGSRR TNPFGETEDE
SFPEAEDSLL QQMFIVRFLG SMAVKTDSTT EVIYEAMRQV LAARAIHNIF RMTESHLMVT
SQSLRLIDPQ TQVSRANFEL TSVTQFAAHQ ENKRLVGFVI RVPESTGEES LSTYIFESNS
EGEKICYAIN LGKEIIEVQK DPEALAQLML SIPLTNDGKY VLLNDQPDDD DGNPNEHRGA
ESEA*

speed

0.55 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

polymorphism

Model: simple_aae, prob: 0.999999998661837 (classification due to TGP/ExAC, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
homozygous in TGP or ExAC
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr12:105583877G>AN/A show variant in all transcripts IGV

HGNC symbol

APPL2

Ensembl transcript ID

ENST00000551662

Genbank transcript ID

N/A

UniProt peptide

Q8NEU8

alteration type

single base exchange

alteration region

CDS

DNA changes

c.1316C>T
cDNA.1387C>T
g.46140C>T

AA changes

A439V Score: 64 explain score(s)

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

439

frameshift

known variant

Reference ID: rs2272495

database	homozygous (A/A)	heterozygous	allele carriers
1000G	107	724	831
ExAC	2605	19402	22007

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	0.186	0
	1.488	0.003
(flanking)	0.43	0.001

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	46133	wt: 0.81 / mu: 0.93	wt: TTGTTCCCAAAGCAA mu: TTGTTCCCAAAGTAA	GTTC\|ccaa
Donor increased	46143	wt: 0.24 / mu: 0.33	wt: AGCAACAGCCAGTCT mu: AGTAACAGCCAGTCT	CAAC\|agcc

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

439

mutated

not conserved

439

Ptroglodytes

all identical

ENSPTRG00000005384

433

Mmulatta

all identical

ENSMMUG00000009524

418

Fcatus

all identical

ENSFCAG00000001461

430

Mmusculus

all identical

ENSMUSG00000020263

433

Ggallus

not conserved

ENSGALG00000012665

433

Trubripes

not conserved

ENSTRUG00000016642

432

Drerio

all conserved

ENSDARG00000078139

432

Dmelanogaster

no homologue

Celegans

no homologue

Xtropicalis

not conserved

ENSXETG00000001888

433

protein features

start (aa)	end (aa)	feature	details
448	448	CONFLICT	T -> A (in Ref. 2).	might get lost (downstream of altered splice site)
488	637	DOMAIN	PID.	might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

2013 / 2013

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

671 / 671

position of stopcodon in wt / mu cDNA

2084 / 2084

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

72 / 72

chromosome

strand

-1

last intron/exon boundary

1950

theoretical NMD boundary in CDS

1828

length of CDS

2013

coding sequence (CDS) position

1316

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

1387

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

46140

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

105583877

original gDNA sequence snippet

TGACAAGATTGTTCCCAAAGCAACAGCCAGTCTACCTGAAG

altered gDNA sequence snippet

TGACAAGATTGTTCCCAAAGTAACAGCCAGTCTACCTGAAG

original cDNA sequence snippet

TGACAAGATTGTTCCCAAAGCAACAGCCAGTCTACCTGAAG

altered cDNA sequence snippet

TGACAAGATTGTTCCCAAAGTAACAGCCAGTCTACCTGAAG

wildtype AA sequence

MPAVDKLLLE EALQDSPQTR SLLSVFEEDA GTLTDYTNQL LQAMQRVYGA QNEMCLATQQ
LSKQLLAYEK QNFALGKGDE EVISTLHYFS KVVDELNLLH TELAKQLADT MVLPIIQFRE
KDLTEVSTLK DLFGLASNDV CLFLEHDLSM AKYSRLPKKK ENEKVKTEVG KEVAAARRKQ
HLSSLQYYCA LNALQYRKQM AMMEPMIGFA HGQINFFKKG AEMFSKRMDS FLSSVADMVQ
SIQVELEAEA EKMRVSQQEL LSVDESVYTP DSDVAAPQIN RNLIQKAGYL NLRNKTGLVT
TTWERLYFFT QGGNLMCQPR GAVAGGLIQD LDNCSVMAVD CEDRRYCFQI TTPNGKSGII
LQAESRKENE EWICAINNIS RQIYLTDNPE AVAIKLNQTA LQAVTPITSF GKKQESSCPS
QNLKNSEMEN ENDKIVPKAT ASLPEAEELI APGTPIQFDI VLPATEFLDQ NRGSRRTNPF
GETEDESFPE AEDSLLQQMF IVRFLGSMAV KTDSTTEVIY EAMRQVLAAR AIHNIFRMTE
SHLMVTSQSL RLIDPQTQVS RANFELTSVT QFAAHQENKR LVGFVIRVPE STGEESLSTY
IFESNSEGEK ICYAINLGKE IIEVQKDPEA LAQLMLSIPL TNDGKYVLLN DQPDDDDGNP
NEHRGAESEA *

mutated AA sequence

MPAVDKLLLE EALQDSPQTR SLLSVFEEDA GTLTDYTNQL LQAMQRVYGA QNEMCLATQQ
LSKQLLAYEK QNFALGKGDE EVISTLHYFS KVVDELNLLH TELAKQLADT MVLPIIQFRE
KDLTEVSTLK DLFGLASNDV CLFLEHDLSM AKYSRLPKKK ENEKVKTEVG KEVAAARRKQ
HLSSLQYYCA LNALQYRKQM AMMEPMIGFA HGQINFFKKG AEMFSKRMDS FLSSVADMVQ
SIQVELEAEA EKMRVSQQEL LSVDESVYTP DSDVAAPQIN RNLIQKAGYL NLRNKTGLVT
TTWERLYFFT QGGNLMCQPR GAVAGGLIQD LDNCSVMAVD CEDRRYCFQI TTPNGKSGII
LQAESRKENE EWICAINNIS RQIYLTDNPE AVAIKLNQTA LQAVTPITSF GKKQESSCPS
QNLKNSEMEN ENDKIVPKVT ASLPEAEELI APGTPIQFDI VLPATEFLDQ NRGSRRTNPF
GETEDESFPE AEDSLLQQMF IVRFLGSMAV KTDSTTEVIY EAMRQVLAAR AIHNIFRMTE
SHLMVTSQSL RLIDPQTQVS RANFELTSVT QFAAHQENKR LVGFVIRVPE STGEESLSTY
IFESNSEGEK ICYAINLGKE IIEVQKDPEA LAQLMLSIPL TNDGKYVLLN DQPDDDDGNP
NEHRGAESEA *

speed

1.34 s

mutation t@sting

documentation

Prediction

polymorphism

Model: simple_aae, prob: 0.9999999982576 (classification due to TGP/ExAC, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
homozygous in TGP or ExAC
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr12:105583877G>AN/A show variant in all transcripts IGV

HGNC symbol

APPL2

Ensembl transcript ID

ENST00000539978

Genbank transcript ID

N/A

UniProt peptide

Q8NEU8

alteration type

single base exchange

alteration region

CDS

DNA changes

c.1169C>T
cDNA.1604C>T
g.46140C>T

AA changes

A390V Score: 64 explain score(s)

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

390

frameshift

known variant

Reference ID: rs2272495

database	homozygous (A/A)	heterozygous	allele carriers
1000G	107	724	831
ExAC	2605	19402	22007

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	0.186	0
	1.488	0.003
(flanking)	0.43	0.001

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	46133	wt: 0.81 / mu: 0.93	wt: TTGTTCCCAAAGCAA mu: TTGTTCCCAAAGTAA	GTTC\|ccaa
Donor increased	46143	wt: 0.24 / mu: 0.33	wt: AGCAACAGCCAGTCT mu: AGTAACAGCCAGTCT	CAAC\|agcc

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

390

mutated

not conserved

390

Ptroglodytes

all identical

ENSPTRG00000005384

433

Mmulatta

all identical

ENSMMUG00000009524

420

Fcatus

all identical

ENSFCAG00000001461

430

Mmusculus

all identical

ENSMUSG00000020263

433

Ggallus

not conserved

ENSGALG00000012665

433

Trubripes

not conserved

ENSTRUG00000016642

432

Drerio

all conserved

ENSDARG00000078139

432

Dmelanogaster

no homologue

Celegans

no homologue

Xtropicalis

not conserved

ENSXETG00000001888

433

protein features

start (aa)	end (aa)	feature	details
1	428	REGION	Required for RAB5A binding (By similarity).	lost
448	448	CONFLICT	T -> A (in Ref. 2).	might get lost (downstream of altered splice site)
488	637	DOMAIN	PID.	might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

1866 / 1866

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

622 / 622

position of stopcodon in wt / mu cDNA

2301 / 2301

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

436 / 436

chromosome

strand

-1

last intron/exon boundary

2167

theoretical NMD boundary in CDS

1681

length of CDS

1866

coding sequence (CDS) position

1169

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

1604

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

46140

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

105583877

original gDNA sequence snippet

TGACAAGATTGTTCCCAAAGCAACAGCCAGTCTACCTGAAG

altered gDNA sequence snippet

TGACAAGATTGTTCCCAAAGTAACAGCCAGTCTACCTGAAG

original cDNA sequence snippet

TGACAAGATTGTTCCCAAAGCAACAGCCAGTCTACCTGAAG

altered cDNA sequence snippet

TGACAAGATTGTTCCCAAAGTAACAGCCAGTCTACCTGAAG

wildtype AA sequence

MQRVYGAQNE MCLATQQLSK QLLAYEKQNF ALGKGDEEVI STLHYFSKVV DELNLLHTEL
AKQLADTMVL PIIQFREKDL TEVSTLKDLF GLASNEHDLS MAKYSRLPKK KENEKVKTEV
GKEVAAARRK QHLSSLQYYC ALNALQYRKQ MAMMEPMIGF AHGQINFFKK GAEMFSKRMD
SFLSSVADMV QSIQVELEAE AEKMRVSQQE LLSVDESVYT PDSDVAAPQI NRNLIQKAGY
LNLRNKTGLV TTTWERLYFF TQGGNLMCQP RGAVAGGLIQ DLDNCSVMAV DCEDRRYCFQ
ITTPNGKSGI ILQAESRKEN EEWICAINNI SRQIYLTDNP EAVAIKLNQT ALQAVTPITS
FGKKQESSCP SQNLKNSEME NENDKIVPKA TASLPEAEEL IAPGTPIQFD IVLPATEFLD
QNRGSRRTNP FGETEDESFP EAEDSLLQQM FIVRFLGSMA VKTDSTTEVI YEAMRQVLAA
RAIHNIFRMT ESHLMVTSQS LRLIDPQTQV SRANFELTSV TQFAAHQENK RLVGFVIRVP
ESTGEESLST YIFESNSEGE KICYAINLGK EIIEVQKDPE ALAQLMLSIP LTNDGKYVLL
NDQPDDDDGN PNEHRGAESE A*

mutated AA sequence

MQRVYGAQNE MCLATQQLSK QLLAYEKQNF ALGKGDEEVI STLHYFSKVV DELNLLHTEL
AKQLADTMVL PIIQFREKDL TEVSTLKDLF GLASNEHDLS MAKYSRLPKK KENEKVKTEV
GKEVAAARRK QHLSSLQYYC ALNALQYRKQ MAMMEPMIGF AHGQINFFKK GAEMFSKRMD
SFLSSVADMV QSIQVELEAE AEKMRVSQQE LLSVDESVYT PDSDVAAPQI NRNLIQKAGY
LNLRNKTGLV TTTWERLYFF TQGGNLMCQP RGAVAGGLIQ DLDNCSVMAV DCEDRRYCFQ
ITTPNGKSGI ILQAESRKEN EEWICAINNI SRQIYLTDNP EAVAIKLNQT ALQAVTPITS
FGKKQESSCP SQNLKNSEME NENDKIVPKV TASLPEAEEL IAPGTPIQFD IVLPATEFLD
QNRGSRRTNP FGETEDESFP EAEDSLLQQM FIVRFLGSMA VKTDSTTEVI YEAMRQVLAA
RAIHNIFRMT ESHLMVTSQS LRLIDPQTQV SRANFELTSV TQFAAHQENK RLVGFVIRVP
ESTGEESLST YIFESNSEGE KICYAINLGK EIIEVQKDPE ALAQLMLSIP LTNDGKYVLL
NDQPDDDDGN PNEHRGAESE A*

speed

0.99 s

MutationTaster - study a chromosomal position

Results

Taster files

mutation t@sting

Prediction

polymorphism

mutation t@sting

Prediction

polymorphism

mutation t@sting

Prediction

polymorphism

Problems