MutationTaster - study a chromosomal position

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input seems to be ok - now mapping the variant to the different transcripts...
found 4 transcript(s)...
Querying Taster for transcript #1: ENST00000377270
Querying Taster for transcript #2: ENST00000396366
Querying Taster for transcript #3: ENST00000498653
Querying Taster for transcript #4: ENST00000396364
MT speed 0 s - this script 4.189854 s

Results

genesymbol	prediction	probability	model	prediction problem	splicing	ClinVar	amino acid changes	variant type	dbSNP ID	protein length	file
FXN	disease_causing	0.999997830803347	simple_aae		affected		H183R	single base exchange	rs144610605		show file
FXN	disease_causing	0.999997830803347	simple_aae		affected		H108R	single base exchange	rs144610605		show file
FXN	disease_causing	1	without_aae		affected			single base exchange	rs144610605		show file
FXN	polymorphism	0.409055348973659	simple_aae		affected		M186V	single base exchange	rs144610605		show file

Taster files

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999997830803347 (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM993651)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr9:71687593A>GN/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.548A>G
cDNA.1072A>G
g.37419A>G

AA changes

H183R Score: 29 explain score(s)

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

183

frameshift

known variant

Reference ID: rs144610605
Allele 'G' was neither found in ExAC nor 1000G.
known disease mutation at this position, please check HGMD for details (HGMD ID CM993651)

known disease mutation at this position, please check HGMD for details (HGMD ID CM993651)
known disease mutation at this position, please check HGMD for details (HGMD ID CM993651)

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	3.823	1
	4.472	1
(flanking)	-0.208	0.929

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	37422	wt: 0.9675 / mu: 0.9721 (marginal change - not scored)	wt: CGACGGCGTGTCCCTCCATGAGCTGCTGGCCGCAGAGCTCA mu: CGACGGCGTGTCCCTCCGTGAGCTGCTGGCCGCAGAGCTCA	atga\|GCTG
Acc marginally increased	37420	wt: 0.5334 / mu: 0.5402 (marginal change - not scored)	wt: CACGACGGCGTGTCCCTCCATGAGCTGCTGGCCGCAGAGCT mu: CACGACGGCGTGTCCCTCCGTGAGCTGCTGGCCGCAGAGCT	ccat\|GAGC
Acc increased	37418	wt: 0.22 / mu: 0.56	wt: CCCACGACGGCGTGTCCCTCCATGAGCTGCTGGCCGCAGAG mu: CCCACGACGGCGTGTCCCTCCGTGAGCTGCTGGCCGCAGAG	ctcc\|ATGA

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

183

mutated

not conserved

183

Ptroglodytes

no homologue

Mmulatta

all identical

ENSMMUG00000000357

183

Fcatus

all identical

ENSFCAG00000008813

180

Mmusculus

all identical

ENSMUSG00000059363

180

Ggallus

no homologue

Trubripes

no homologue

Drerio

all identical

ENSDARG00000074356

177

Dmelanogaster

all identical

FBgn0030092

161

Celegans

not conserved

F59G1.7

113

Xtropicalis

no homologue

protein features

start (aa)	end (aa)	feature	details
182	194	HELIX		lost
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

548

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

1072

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

37419

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

71687593

original gDNA sequence snippet

CCACGACGGCGTGTCCCTCCATGAGCTGCTGGCCGCAGAGC

altered gDNA sequence snippet

CCACGACGGCGTGTCCCTCCGTGAGCTGCTGGCCGCAGAGC

original cDNA sequence snippet

CCACGACGGCGTGTCCCTCCATGAGCTGCTGGCCGCAGAGC

altered cDNA sequence snippet

CCACGACGGCGTGTCCCTCCGTGAGCTGCTGGCCGCAGAGC

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

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: simple_aae, prob: 0.999997830803347 (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM993651)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr9:71687593A>GN/A show variant in all transcripts IGV

HGNC symbol

FXN

Ensembl transcript ID

ENST00000498653

Genbank transcript ID

N/A

UniProt peptide

Q16595

alteration type

single base exchange

alteration region

CDS

DNA changes

c.323A>G
cDNA.428A>G
g.37419A>G

AA changes

H108R Score: 29 explain score(s)

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

108

frameshift

known variant

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	3.823	1
	4.472	1
(flanking)	-0.208	0.929

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	37422	wt: 0.9675 / mu: 0.9721 (marginal change - not scored)	wt: CGACGGCGTGTCCCTCCATGAGCTGCTGGCCGCAGAGCTCA mu: CGACGGCGTGTCCCTCCGTGAGCTGCTGGCCGCAGAGCTCA	atga\|GCTG
Acc marginally increased	37420	wt: 0.5334 / mu: 0.5402 (marginal change - not scored)	wt: CACGACGGCGTGTCCCTCCATGAGCTGCTGGCCGCAGAGCT mu: CACGACGGCGTGTCCCTCCGTGAGCTGCTGGCCGCAGAGCT	ccat\|GAGC
Acc increased	37418	wt: 0.22 / mu: 0.56	wt: CCCACGACGGCGTGTCCCTCCATGAGCTGCTGGCCGCAGAG mu: CCCACGACGGCGTGTCCCTCCGTGAGCTGCTGGCCGCAGAG	ctcc\|ATGA

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

108

mutated

not conserved

108

Ptroglodytes

no homologue

Mmulatta

all identical

ENSMMUG00000000357

183

Fcatus

all identical

ENSFCAG00000008813

181

Mmusculus

all identical

ENSMUSG00000059363

180

Ggallus

no homologue

Trubripes

no homologue

Drerio

all identical

ENSDARG00000074356

177

Dmelanogaster

all identical

FBgn0030092

161

Celegans

not conserved

F59G1.7

113

Xtropicalis

no homologue

protein features

start (aa)	end (aa)	feature	details
92	114	HELIX		lost
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

408 / 408

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

136 / 136

position of stopcodon in wt / mu cDNA

513 / 513

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

106 / 106

chromosome

strand

last intron/exon boundary

363

theoretical NMD boundary in CDS

207

length of CDS

408

coding sequence (CDS) position

323

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

428

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

37419

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

71687593

original gDNA sequence snippet

CCACGACGGCGTGTCCCTCCATGAGCTGCTGGCCGCAGAGC

altered gDNA sequence snippet

CCACGACGGCGTGTCCCTCCGTGAGCTGCTGGCCGCAGAGC

original cDNA sequence snippet

CCACGACGGCGTGTCCCTCCATGAGCTGCTGGCCGCAGAGC

altered cDNA sequence snippet

CCACGACGGCGTGTCCCTCCGTGAGCTGCTGGCCGCAGAGC

wildtype AA sequence

MNLRKSGTLG HPGSLDETTY ERLAEETLDS LAEFFEDLAD KPYTFEDYDV SFGSGVLTVK
LGGDLGTYVI NKQTPNKQIW LSSPSSGPKR YDWTGKNWVY SHDGVSLHEL LAAELTKALK
TKLDLSSLAY SGKDA*

mutated AA sequence

MNLRKSGTLG HPGSLDETTY ERLAEETLDS LAEFFEDLAD KPYTFEDYDV SFGSGVLTVK
LGGDLGTYVI NKQTPNKQIW LSSPSSGPKR YDWTGKNWVY SHDGVSLREL LAAELTKALK
TKLDLSSLAY SGKDA*

speed

0.76 s

mutation t@sting

documentation

Prediction

disease causing

Model: without_aae, prob: 1 (explain)

Summary

known disease mutation at this position (HGMD CM993651)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr9:71687593A>GN/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

intron

DNA changes

g.37419A>G

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)	3.823	1
	4.472	1
(flanking)	-0.208	0.929

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	37422	wt: 0.9675 / mu: 0.9721 (marginal change - not scored)	wt: CGACGGCGTGTCCCTCCATGAGCTGCTGGCCGCAGAGCTCA mu: CGACGGCGTGTCCCTCCGTGAGCTGCTGGCCGCAGAGCTCA	atga\|GCTG
Acc marginally increased	37420	wt: 0.5334 / mu: 0.5402 (marginal change - not scored)	wt: CACGACGGCGTGTCCCTCCATGAGCTGCTGGCCGCAGAGCT mu: CACGACGGCGTGTCCCTCCGTGAGCTGCTGGCCGCAGAGCT	ccat\|GAGC
Acc increased	37418	wt: 0.22 / mu: 0.56	wt: CCCACGACGGCGTGTCCCTCCATGAGCTGCTGGCCGCAGAG mu: CCCACGACGGCGTGTCCCTCCGTGAGCTGCTGGCCGCAGAG	ctcc\|ATGA

distance from splice site

7642

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

N/A

protein features

start (aa)	end (aa)	feature	details
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

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

221 / 221

chromosome

strand

last intron/exon boundary

703

theoretical NMD boundary in CDS

432

length of CDS

516

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)

37419

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

71687593

original gDNA sequence snippet

CCACGACGGCGTGTCCCTCCATGAGCTGCTGGCCGCAGAGC

altered gDNA sequence snippet

CCACGACGGCGTGTCCCTCCGTGAGCTGCTGGCCGCAGAGC

original cDNA sequence snippet

N/A

altered cDNA sequence snippet

N/A

wildtype AA sequence

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

mutated AA sequence

N/A

speed

0.45 s

mutation t@sting

documentation

Prediction

polymorphism

Model: simple_aae, prob: 0.590944651026341 (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM993651)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr9:71687593A>GN/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.556A>G
cDNA.577A>G
g.37419A>G

AA changes

M186V Score: 21 explain score(s)

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

186

frameshift

known variant

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	3.823	1
	4.472	1
(flanking)	-0.208	0.929

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	37422	wt: 0.9675 / mu: 0.9721 (marginal change - not scored)	wt: CGACGGCGTGTCCCTCCATGAGCTGCTGGCCGCAGAGCTCA mu: CGACGGCGTGTCCCTCCGTGAGCTGCTGGCCGCAGAGCTCA	atga\|GCTG
Acc marginally increased	37420	wt: 0.5334 / mu: 0.5402 (marginal change - not scored)	wt: CACGACGGCGTGTCCCTCCATGAGCTGCTGGCCGCAGAGCT mu: CACGACGGCGTGTCCCTCCGTGAGCTGCTGGCCGCAGAGCT	ccat\|GAGC
Acc increased	37418	wt: 0.22 / mu: 0.56	wt: CCCACGACGGCGTGTCCCTCCATGAGCTGCTGGCCGCAGAG mu: CCCACGACGGCGTGTCCCTCCGTGAGCTGCTGGCCGCAGAG	ctcc\|ATGA

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

186

mutated

all conserved

186

Ptroglodytes

no homologue

Mmulatta

no alignment

ENSMMUG00000000357

n/a

Fcatus

no alignment

ENSFCAG00000008813

n/a

Mmusculus

no alignment

ENSMUSG00000059363

n/a

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
182	194	HELIX		lost
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

556

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

577

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

37419

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

71687593

original gDNA sequence snippet

CCACGACGGCGTGTCCCTCCATGAGCTGCTGGCCGCAGAGC

altered gDNA sequence snippet

CCACGACGGCGTGTCCCTCCGTGAGCTGCTGGCCGCAGAGC

original cDNA sequence snippet

CCACGACGGCGTGTCCCTCCATGAGCTGCTGGCCGCAGAGC

altered cDNA sequence snippet

CCACGACGGCGTGTCCCTCCGTGAGCTGCTGGCCGCAGAGC

wildtype AA sequence

mutated AA sequence

speed

0.90 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

mutation t@sting

Prediction

polymorphism

Problems