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 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 4.528424 s

Results

genesymbol	prediction	probability	model	prediction problem	splicing	ClinVar	amino acid changes	variant type	dbSNP ID	protein length	file
FXN	disease_causing	0.999944136957386	simple_aae		affected		D122Y	single base exchange	rs142157346		show file
FXN	disease_causing	0.999944136957386	simple_aae		affected		D122Y	single base exchange	rs142157346		show file
FXN	disease_causing	0.999944136957386	simple_aae		affected		D47Y	single base exchange	rs142157346		show file
FXN	disease_causing	0.999944136957386	simple_aae		affected		D122Y	single base exchange	rs142157346		show file

Taster files

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999944136957386 (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM993647)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr9:71668156G>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.364G>T
cDNA.385G>T
g.17982G>T

AA changes

D122Y Score: 160 explain score(s)

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

122

frameshift

known variant

Reference ID: rs142157346
Allele 'T' was neither found in ExAC nor 1000G.
known disease mutation at this position, please check HGMD for details (HGMD ID CM993647)

known disease mutation at this position, please check HGMD for details (HGMD ID CM993647)
known disease mutation at this position, please check HGMD for details (HGMD ID CM993647)

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation
H4K20me1, Histone, Histone 4 Lysine 20 mono-methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	0.321	0.968
	3.953	1
(flanking)	3.297	1

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	17975	wt: 0.57 / mu: 0.96	wt: TACACGTTTGAGGAC mu: TACACGTTTGAGTAC	CACG\|tttg
Donor increased	17985	wt: 0.85 / mu: 0.94	wt: AGGACTATGATGTCT mu: AGTACTATGATGTCT	GACT\|atga

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

122

mutated

not conserved

122

Ptroglodytes

no homologue

Mmulatta

all identical

ENSMMUG00000000357

122

Fcatus

all identical

ENSFCAG00000008813

120

Mmusculus

all identical

ENSMUSG00000059363

119

Ggallus

no homologue

Trubripes

no homologue

Drerio

all identical

ENSDARG00000074356

116

Dmelanogaster

not conserved

FBgn0030092

100

Celegans

not conserved

F59G1.7

Xtropicalis

no homologue

protein features

start (aa)	end (aa)	feature	details
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

364

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

385

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

17982

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

71668156

original gDNA sequence snippet

ACAAGCCATACACGTTTGAGGACTATGATGTCTCCTTTGGG

altered gDNA sequence snippet

ACAAGCCATACACGTTTGAGTACTATGATGTCTCCTTTGGG

original cDNA sequence snippet

ACAAGCCATACACGTTTGAGGACTATGATGTCTCCTTTGGG

altered cDNA sequence snippet

ACAAGCCATACACGTTTGAGTACTATGATGTCTCCTTTGGG

wildtype AA sequence

MWTLGRRAVA GLLASPSPAQ AQTLTRVPRP AELAPLCGRR GLRTDIDATC TPRRASSNQR
GLNQIWNVKK QSVYLMNLRK SGTLGHPGSL DETTYERLAE ETLDSLAEFF EDLADKPYTF
EDYDVSFGSG VLTVKLGGDL GTYVINKQTP NKQIWLSSPS RYVVDLSVMT GLGKTGCTPT
TACPSMSCWP QSSLKP*

mutated AA sequence

MWTLGRRAVA GLLASPSPAQ AQTLTRVPRP AELAPLCGRR GLRTDIDATC TPRRASSNQR
GLNQIWNVKK QSVYLMNLRK SGTLGHPGSL DETTYERLAE ETLDSLAEFF EDLADKPYTF
EYYDVSFGSG VLTVKLGGDL GTYVINKQTP NKQIWLSSPS RYVVDLSVMT GLGKTGCTPT
TACPSMSCWP QSSLKP*

speed

0.86 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: 0.999944136957386 (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM993647)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr9:71668156G>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.364G>T
cDNA.888G>T
g.17982G>T

AA changes

D122Y Score: 160 explain score(s)

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

122

frameshift

known variant

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation
H4K20me1, Histone, Histone 4 Lysine 20 mono-methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	0.321	0.968
	3.953	1
(flanking)	3.297	1

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	17975	wt: 0.57 / mu: 0.96	wt: TACACGTTTGAGGAC mu: TACACGTTTGAGTAC	CACG\|tttg
Donor increased	17985	wt: 0.85 / mu: 0.94	wt: AGGACTATGATGTCT mu: AGTACTATGATGTCT	GACT\|atga

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

122

mutated

not conserved

122

Ptroglodytes

no homologue

Mmulatta

all identical

ENSMMUG00000000357

122

Fcatus

all identical

ENSFCAG00000008813

120

Mmusculus

all identical

ENSMUSG00000059363

119

Ggallus

no homologue

Trubripes

no homologue

Drerio

all identical

ENSDARG00000074356

116

Dmelanogaster

not conserved

FBgn0030092

100

Celegans

not conserved

F59G1.7

Xtropicalis

no homologue

protein features

start (aa)	end (aa)	feature	details
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

364

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

888

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

17982

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

71668156

original gDNA sequence snippet

ACAAGCCATACACGTTTGAGGACTATGATGTCTCCTTTGGG

altered gDNA sequence snippet

ACAAGCCATACACGTTTGAGTACTATGATGTCTCCTTTGGG

original cDNA sequence snippet

ACAAGCCATACACGTTTGAGGACTATGATGTCTCCTTTGGG

altered cDNA sequence snippet

ACAAGCCATACACGTTTGAGTACTATGATGTCTCCTTTGGG

wildtype AA sequence

mutated AA sequence

speed

0.85 s

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999944136957386 (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM993647)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr9:71668156G>TN/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.139G>T
cDNA.244G>T
g.17982G>T

AA changes

D47Y Score: 160 explain score(s)

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

frameshift

known variant

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation
H4K20me1, Histone, Histone 4 Lysine 20 mono-methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	0.321	0.968
	3.953	1
(flanking)	3.297	1

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	17975	wt: 0.57 / mu: 0.96	wt: TACACGTTTGAGGAC mu: TACACGTTTGAGTAC	CACG\|tttg
Donor increased	17985	wt: 0.85 / mu: 0.94	wt: AGGACTATGATGTCT mu: AGTACTATGATGTCT	GACT\|atga

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

122

Fcatus

all identical

ENSFCAG00000008813

120

Mmusculus

all identical

ENSMUSG00000059363

119

Ggallus

no homologue

Trubripes

no homologue

Drerio

all identical

ENSDARG00000074356

116

Dmelanogaster

not conserved

FBgn0030092

100

Celegans

not conserved

F59G1.7

Xtropicalis

no homologue

protein features

start (aa)	end (aa)	feature	details
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

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

139

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

244

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

17982

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

71668156

original gDNA sequence snippet

ACAAGCCATACACGTTTGAGGACTATGATGTCTCCTTTGGG

altered gDNA sequence snippet

ACAAGCCATACACGTTTGAGTACTATGATGTCTCCTTTGGG

original cDNA sequence snippet

ACAAGCCATACACGTTTGAGGACTATGATGTCTCCTTTGGG

altered cDNA sequence snippet

ACAAGCCATACACGTTTGAGTACTATGATGTCTCCTTTGGG

wildtype AA sequence

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

mutated AA sequence

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

speed

0.78 s

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999944136957386 (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM993647)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr9:71668156G>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.364G>T
cDNA.584G>T
g.17982G>T

AA changes

D122Y Score: 160 explain score(s)

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

122

frameshift

known variant

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation
H4K20me1, Histone, Histone 4 Lysine 20 mono-methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	0.321	0.968
	3.953	1
(flanking)	3.297	1

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	17975	wt: 0.57 / mu: 0.96	wt: TACACGTTTGAGGAC mu: TACACGTTTGAGTAC	CACG\|tttg
Donor increased	17985	wt: 0.85 / mu: 0.94	wt: AGGACTATGATGTCT mu: AGTACTATGATGTCT	GACT\|atga

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

122

mutated

not conserved

122

Ptroglodytes

no homologue

Mmulatta

all identical

ENSMMUG00000000357

122

Fcatus

all identical

ENSFCAG00000008813

120

Mmusculus

all identical

ENSMUSG00000059363

119

Ggallus

no homologue

Trubripes

no homologue

Drerio

all identical

ENSDARG00000074356

116

Dmelanogaster

not conserved

FBgn0030092

100

Celegans

not conserved

F59G1.7

Xtropicalis

no homologue

protein features

start (aa)	end (aa)	feature	details
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

364

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

584

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

17982

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

71668156

original gDNA sequence snippet

ACAAGCCATACACGTTTGAGGACTATGATGTCTCCTTTGGG

altered gDNA sequence snippet

ACAAGCCATACACGTTTGAGTACTATGATGTCTCCTTTGGG

original cDNA sequence snippet

ACAAGCCATACACGTTTGAGGACTATGATGTCTCCTTTGGG

altered cDNA sequence snippet

ACAAGCCATACACGTTTGAGTACTATGATGTCTCCTTTGGG

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 AELAPLCGRR GLRTDIDATC TPRRASSNQR
GLNQIWNVKK QSVYLMNLRK SGTLGHPGSL DETTYERLAE ETLDSLAEFF EDLADKPYTF
EYYDVSFGSG VLTVKLGGDL GTYVINKQTP NKQIWLSSPS RLTWLLWLFH P*

speed

0.76 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

disease causing

Problems