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 3 transcript(s)...
Querying Taster for transcript #1: ENST00000377270
Querying Taster for transcript #2: ENST00000396366
Querying Taster for transcript #3: ENST00000396364
MT speed 1.84 s - this script 3.539722 s

Results

genesymbol	prediction	probability	model	prediction problem	splicing	ClinVar	amino acid changes	variant type	dbSNP ID	protein length	file
FXN	disease_causing_automatic	7.64294046404004e-08	simple_aae		affected	0	R40C	single base exchange	rs145854903		show file
FXN	disease_causing_automatic	7.64294046404004e-08	simple_aae		affected	0	R40C	single base exchange	rs145854903		show file
FXN	disease_causing_automatic	7.64294046404004e-08	simple_aae		affected	0	R40C	single base exchange	rs145854903		show file

Taster files

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 7.64294046404004e-08 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CD000263)
known disease mutation at this position (HGMD CM052877)
known disease mutation: rs264451 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr9:71650816C>TN/A show variant in all transcripts IGV

HGNC symbol

FXN

Ensembl transcript ID

ENST00000377270

Genbank transcript ID

NM_000144

UniProt peptide

Q16595

alteration type

single base exchange

alteration region

CDS

DNA changes

c.118C>T
cDNA.642C>T
g.642C>T

AA changes

R40C Score: 180 explain score(s)

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

frameshift

known variant

Reference ID: rs145854903
Allele 'T' was neither found in ExAC nor 1000G.
known disease mutation: rs264451 (pathogenic for Hypertrophic cardiomyopathy|not specified|Cardiovascular phenotype) dbSNP NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CD000263)

known disease mutation at this position, please check HGMD for details (HGMD ID CD000263)
known disease mutation at this position, please check HGMD for details (HGMD ID CM052877)

known disease mutation at this position, please check HGMD for details (HGMD ID CD000263)
known disease mutation at this position, please check HGMD for details (HGMD ID CM052877)
known disease mutation at this position, please check HGMD for details (HGMD ID CD000263)

known disease mutation at this position, please check HGMD for details (HGMD ID CD000263)
known disease mutation at this position, please check HGMD for details (HGMD ID CM052877)
known disease mutation at this position, please check HGMD for details (HGMD ID CD000263)
known disease mutation at this position, please check HGMD for details (HGMD ID CM052877)

regulatory features

Ap2alpha, Transcription Factor, Ap2alpha Transcription Factor Binding
CTCF, Transcription Factor, CCCTC-binding factor
Cmyc, Transcription Factor, Cmyc TF binding
DNase1, Open Chromatin, DNase1 Hypersensitive Site
E2F1, Transcription Factor, E2F1 Transcription Factor Binding
E2F6, Transcription Factor, E2F6 Transcription Factor Binding
ELF1, Transcription Factor, ELF1 Transcription Factor Binding
Egr1, Transcription Factor, Egr1 Transcription Factor Binding
H2AZ, Histone, Histone 2A variant Z
H3K27ac, Histone, Histone 3 Lysine 27 Acetylation
H3K27me3, Histone, Histone 3 Lysine 27 Tri-Methylation
H3K4me2, Histone, Histone 3 Lysine 4 Di-Methylation
H3K4me3, Histone, Histone 3 Lysine 4 Tri-Methylation
H3K9ac, Histone, Histone 3 Lysine 9 Acetylation
HEY1, Transcription Factor, HEY1 Transcription Factor Binding
HNF4A, Transcription Factor, HNF4A Transcription Factor Binding
Max, Transcription Factor, Max TF binding
PolII, Polymerase, RNA Polymerase II
Promoter Associated, Regulatory Feature, Promoter like regulatory feature
Rad21, Transcription Factor, Rad21 Transcription Factor Binding
Sin3Ak20, Transcription Factor, Sin3Ak20 Transcription Factor Binding
TAF1, Transcription Factor, TAF1 Transcription Factor Binding
Yy1, Transcription Factor, Yy1 Transcription Factor Binding

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	0.149	0.001
	1.586	0.002
(flanking)	-0.236	0

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 gained	653	0.30	mu: TGCGGCCGCTGTGGCCTGCGCACCGACATCGATGCGACCTG	gcgc\|ACCG

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

mutated

not conserved

Ptroglodytes

no homologue

Mmulatta

all identical

ENSMMUG00000000357

Fcatus

all identical

ENSFCAG00000008813

Mmusculus

all identical

ENSMUSG00000059363

Ggallus

no homologue

Trubripes

no homologue

Drerio

no alignment

ENSDARG00000074356

n/a

Dmelanogaster

no alignment

FBgn0030092

n/a

Celegans

no alignment

F59G1.7

n/a

Xtropicalis

no homologue

protein features

start (aa)	end (aa)	feature	details
1	41	TRANSIT	Mitochondrion.	lost
39	40	MUTAGEN	RR->GG: Abolishes cleavage to yield frataxin intermediate form and allows accumulation of frataxin(56-210) and frataxin(78-210).	lost
53	54	MUTAGEN	RR->GG: No effect on processing of wild- type FXN.	might get lost (downstream of altered splice site)
78	79	MUTAGEN	LR->GG: Abolishes cleavage to yield frataxin mature form and allows accumulation of frataxin(56-210) and frataxin(78-210).	might get lost (downstream of altered splice site)
79	80	MUTAGEN	RK->GG: Abolishes cleavage to yield frataxin mature form and allows the accumulation of frataxin(56-210).	might get lost (downstream of altered splice site)
92	114	HELIX		might get lost (downstream of altered splice site)
124	128	STRAND		might get lost (downstream of altered splice site)
131	135	STRAND		might get lost (downstream of altered splice site)
138	140	TURN		might get lost (downstream of altered splice site)
142	148	STRAND		might get lost (downstream of altered splice site)
149	152	TURN		might get lost (downstream of altered splice site)
153	157	STRAND		might get lost (downstream of altered splice site)
159	161	STRAND		might get lost (downstream of altered splice site)
164	168	STRAND		might get lost (downstream of altered splice site)
170	175	STRAND		might get lost (downstream of altered splice site)
175	175	CONFLICT	Y -> F (in Ref. 1; AAA98508/AAA98510).	might get lost (downstream of altered splice site)
176	178	TURN		might get lost (downstream of altered splice site)
182	194	HELIX		might get lost (downstream of altered splice site)
202	202	CONFLICT	S -> W (in Ref. 1; AAA98508/AAA98510).	might get lost (downstream of altered splice site)
206	208	STRAND		might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

633 / 633

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

211 / 211

position of stopcodon in wt / mu cDNA

1157 / 1157

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

525 / 525

chromosome

strand

last intron/exon boundary

1007

theoretical NMD boundary in CDS

432

length of CDS

633

coding sequence (CDS) position

118

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

642

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

642

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

71650816

original gDNA sequence snippet

TGGCCCCACTCTGCGGCCGCCGTGGCCTGCGCACCGACATC

altered gDNA sequence snippet

TGGCCCCACTCTGCGGCCGCTGTGGCCTGCGCACCGACATC

original cDNA sequence snippet

TGGCCCCACTCTGCGGCCGCCGTGGCCTGCGCACCGACATC

altered cDNA sequence snippet

TGGCCCCACTCTGCGGCCGCTGTGGCCTGCGCACCGACATC

wildtype AA sequence

MWTLGRRAVA GLLASPSPAQ AQTLTRVPRP AELAPLCGRR GLRTDIDATC TPRRASSNQR
GLNQIWNVKK QSVYLMNLRK SGTLGHPGSL DETTYERLAE ETLDSLAEFF EDLADKPYTF
EDYDVSFGSG VLTVKLGGDL GTYVINKQTP NKQIWLSSPS SGPKRYDWTG KNWVYSHDGV
SLHELLAAEL TKALKTKLDL SSLAYSGKDA *

mutated AA sequence

MWTLGRRAVA GLLASPSPAQ AQTLTRVPRP AELAPLCGRC GLRTDIDATC TPRRASSNQR
GLNQIWNVKK QSVYLMNLRK SGTLGHPGSL DETTYERLAE ETLDSLAEFF EDLADKPYTF
EDYDVSFGSG VLTVKLGGDL GTYVINKQTP NKQIWLSSPS SGPKRYDWTG KNWVYSHDGV
SLHELLAAEL TKALKTKLDL SSLAYSGKDA *

speed

0.46 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: 7.64294046404004e-08 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CD000263)
known disease mutation at this position (HGMD CM052877)
known disease mutation: rs264451 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr9:71650816C>TN/A show variant in all transcripts IGV

HGNC symbol

FXN

Ensembl transcript ID

ENST00000396366

Genbank transcript ID

NM_181425

UniProt peptide

Q16595

alteration type

single base exchange

alteration region

CDS

DNA changes

c.118C>T
cDNA.139C>T
g.642C>T

AA changes

R40C Score: 180 explain score(s)

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

frameshift

known variant

regulatory features

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	0.149	0.001
	1.586	0.002
(flanking)	-0.236	0

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 gained	653	0.30	mu: TGCGGCCGCTGTGGCCTGCGCACCGACATCGATGCGACCTG	gcgc\|ACCG

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

mutated

not conserved

Ptroglodytes

no homologue

Mmulatta

all identical

ENSMMUG00000000357

Fcatus

all identical

ENSFCAG00000008813

Mmusculus

all identical

ENSMUSG00000059363

Ggallus

no homologue

Trubripes

no homologue

Drerio

no alignment

ENSDARG00000074356

n/a

Dmelanogaster

no alignment

FBgn0030092

n/a

Celegans

no alignment

F59G1.7

n/a

Xtropicalis

no homologue

protein features

start (aa)	end (aa)	feature	details
1	41	TRANSIT	Mitochondrion.	lost
39	40	MUTAGEN	RR->GG: Abolishes cleavage to yield frataxin intermediate form and allows accumulation of frataxin(56-210) and frataxin(78-210).	lost
53	54	MUTAGEN	RR->GG: No effect on processing of wild- type FXN.	might get lost (downstream of altered splice site)
78	79	MUTAGEN	LR->GG: Abolishes cleavage to yield frataxin mature form and allows accumulation of frataxin(56-210) and frataxin(78-210).	might get lost (downstream of altered splice site)
79	80	MUTAGEN	RK->GG: Abolishes cleavage to yield frataxin mature form and allows the accumulation of frataxin(56-210).	might get lost (downstream of altered splice site)
92	114	HELIX		might get lost (downstream of altered splice site)
124	128	STRAND		might get lost (downstream of altered splice site)
131	135	STRAND		might get lost (downstream of altered splice site)
138	140	TURN		might get lost (downstream of altered splice site)
142	148	STRAND		might get lost (downstream of altered splice site)
149	152	TURN		might get lost (downstream of altered splice site)
153	157	STRAND		might get lost (downstream of altered splice site)
159	161	STRAND		might get lost (downstream of altered splice site)
164	168	STRAND		might get lost (downstream of altered splice site)
170	175	STRAND		might get lost (downstream of altered splice site)
175	175	CONFLICT	Y -> F (in Ref. 1; AAA98508/AAA98510).	might get lost (downstream of altered splice site)
176	178	TURN		might get lost (downstream of altered splice site)
182	194	HELIX		might get lost (downstream of altered splice site)
202	202	CONFLICT	S -> W (in Ref. 1; AAA98508/AAA98510).	might get lost (downstream of altered splice site)
206	208	STRAND		might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

591 / 591

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

197 / 197

position of stopcodon in wt / mu cDNA

612 / 612

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

22 / 22

chromosome

strand

last intron/exon boundary

512

theoretical NMD boundary in CDS

440

length of CDS

591

coding sequence (CDS) position

118

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

139

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

642

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

71650816

original gDNA sequence snippet

TGGCCCCACTCTGCGGCCGCCGTGGCCTGCGCACCGACATC

altered gDNA sequence snippet

TGGCCCCACTCTGCGGCCGCTGTGGCCTGCGCACCGACATC

original cDNA sequence snippet

TGGCCCCACTCTGCGGCCGCCGTGGCCTGCGCACCGACATC

altered cDNA sequence snippet

TGGCCCCACTCTGCGGCCGCTGTGGCCTGCGCACCGACATC

wildtype AA sequence

mutated AA sequence

speed

0.45 s

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 7.64294046404004e-08 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CD000263)
known disease mutation at this position (HGMD CM052877)
known disease mutation: rs264451 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr9:71650816C>TN/A show variant in all transcripts IGV

HGNC symbol

FXN

Ensembl transcript ID

ENST00000396364

Genbank transcript ID

NM_001161706

UniProt peptide

Q16595

alteration type

single base exchange

alteration region

CDS

DNA changes

c.118C>T
cDNA.338C>T
g.642C>T

AA changes

R40C Score: 180 explain score(s)

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

frameshift

known variant

regulatory features

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	0.149	0.001
	1.586	0.002
(flanking)	-0.236	0

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 gained	653	0.30	mu: TGCGGCCGCTGTGGCCTGCGCACCGACATCGATGCGACCTG	gcgc\|ACCG

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

mutated

not conserved

Ptroglodytes

no homologue

Mmulatta

all identical

ENSMMUG00000000357

Fcatus

all identical

ENSFCAG00000008813

Mmusculus

all identical

ENSMUSG00000059363

Ggallus

no homologue

Trubripes

no homologue

Drerio

no alignment

ENSDARG00000074356

n/a

Dmelanogaster

no alignment

FBgn0030092

n/a

Celegans

no alignment

F59G1.7

n/a

Xtropicalis

no homologue

protein features

start (aa)	end (aa)	feature	details
1	41	TRANSIT	Mitochondrion.	lost
39	40	MUTAGEN	RR->GG: Abolishes cleavage to yield frataxin intermediate form and allows accumulation of frataxin(56-210) and frataxin(78-210).	lost
53	54	MUTAGEN	RR->GG: No effect on processing of wild- type FXN.	might get lost (downstream of altered splice site)
78	79	MUTAGEN	LR->GG: Abolishes cleavage to yield frataxin mature form and allows accumulation of frataxin(56-210) and frataxin(78-210).	might get lost (downstream of altered splice site)
79	80	MUTAGEN	RK->GG: Abolishes cleavage to yield frataxin mature form and allows the accumulation of frataxin(56-210).	might get lost (downstream of altered splice site)
92	114	HELIX		might get lost (downstream of altered splice site)
124	128	STRAND		might get lost (downstream of altered splice site)
131	135	STRAND		might get lost (downstream of altered splice site)
138	140	TURN		might get lost (downstream of altered splice site)
142	148	STRAND		might get lost (downstream of altered splice site)
149	152	TURN		might get lost (downstream of altered splice site)
153	157	STRAND		might get lost (downstream of altered splice site)
159	161	STRAND		might get lost (downstream of altered splice site)
164	168	STRAND		might get lost (downstream of altered splice site)
170	175	STRAND		might get lost (downstream of altered splice site)
175	175	CONFLICT	Y -> F (in Ref. 1; AAA98508/AAA98510).	might get lost (downstream of altered splice site)
176	178	TURN		might get lost (downstream of altered splice site)
182	194	HELIX		might get lost (downstream of altered splice site)
202	202	CONFLICT	S -> W (in Ref. 1; AAA98508/AAA98510).	might get lost (downstream of altered splice site)
206	208	STRAND		might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

516 / 516

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

172 / 172

position of stopcodon in wt / mu cDNA

736 / 736

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

221 / 221

chromosome

strand

last intron/exon boundary

703

theoretical NMD boundary in CDS

432

length of CDS

516

coding sequence (CDS) position

118

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

338

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

642

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

71650816

original gDNA sequence snippet

TGGCCCCACTCTGCGGCCGCCGTGGCCTGCGCACCGACATC

altered gDNA sequence snippet

TGGCCCCACTCTGCGGCCGCTGTGGCCTGCGCACCGACATC

original cDNA sequence snippet

TGGCCCCACTCTGCGGCCGCCGTGGCCTGCGCACCGACATC

altered cDNA sequence snippet

TGGCCCCACTCTGCGGCCGCTGTGGCCTGCGCACCGACATC

wildtype AA sequence

MWTLGRRAVA GLLASPSPAQ AQTLTRVPRP AELAPLCGRR GLRTDIDATC TPRRASSNQR
GLNQIWNVKK QSVYLMNLRK SGTLGHPGSL DETTYERLAE ETLDSLAEFF EDLADKPYTF
EDYDVSFGSG VLTVKLGGDL GTYVINKQTP NKQIWLSSPS RLTWLLWLFH P*

mutated AA sequence

MWTLGRRAVA GLLASPSPAQ AQTLTRVPRP AELAPLCGRC GLRTDIDATC TPRRASSNQR
GLNQIWNVKK QSVYLMNLRK SGTLGHPGSL DETTYERLAE ETLDSLAEFF EDLADKPYTF
EDYDVSFGSG VLTVKLGGDL GTYVINKQTP NKQIWLSSPS RLTWLLWLFH P*

speed

0.93 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

Problems