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 2 transcript(s)...
Querying Taster for transcript #1: ENST00000252288
Querying Taster for transcript #2: ENST00000447102
MT speed 0 s - this script 3.57003 s

Results

genesymbol	prediction	probability	model	prediction problem	splicing	ClinVar	amino acid changes	variant type	dbSNP ID	protein length	file
GAMT	disease_causing_automatic	0.999999999999999	simple_aae		affected	0	W20S	single base exchange	rs80338734		show file
GAMT	disease_causing_automatic	0.999999999999999	simple_aae		affected	0	W20S	single base exchange	rs80338734		show file

Taster files

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999999999999999 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CI1414351)
known disease mutation at this position (HGMD CM041007)
known disease mutation: rs8303 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr19:1401417C>GN/A show variant in all transcripts IGV

HGNC symbol

GAMT

Ensembl transcript ID

ENST00000252288

Genbank transcript ID

NM_000156

UniProt peptide

Q14353

alteration type

single base exchange

alteration region

CDS

DNA changes

c.59G>C
cDNA.126G>C
g.153G>C

AA changes

W20S Score: 177 explain score(s)

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

frameshift

known variant

Reference ID: rs80338734
Allele 'G' was neither found in ExAC nor 1000G.
known disease mutation: rs8303 (pathogenic for Cerebral creatine deficiency syndrome|Deficiency of guanidinoacetate methyltransferase|not provided) dbSNP NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CI1414351)

known disease mutation at this position, please check HGMD for details (HGMD ID CI1414351)
known disease mutation at this position, please check HGMD for details (HGMD ID CM041007)

known disease mutation at this position, please check HGMD for details (HGMD ID CI1414351)
known disease mutation at this position, please check HGMD for details (HGMD ID CM041007)
known disease mutation at this position, please check HGMD for details (HGMD ID CM041007)

regulatory features

Promoter Associated, Regulatory Feature, Promoter like regulatory feature
H3K4me2, Histone, Histone 3 Lysine 4 Di-Methylation
H3K27me3, Histone, Histone 3 Lysine 27 Tri-Methylation
E2F6, Transcription Factor, E2F6 Transcription Factor Binding
PolII, Polymerase, RNA Polymerase II
HEY1, Transcription Factor, HEY1 Transcription Factor Binding
H3K9ac, Histone, Histone 3 Lysine 9 Acetylation
CTCF, Transcription Factor, CCCTC-binding factor
TAF1, Transcription Factor, TAF1 Transcription Factor Binding
H3K4me3, Histone, Histone 3 Lysine 4 Tri-Methylation
E2F1, Transcription Factor, E2F1 Transcription Factor Binding
TFIIIC-110, Transcription Factor, TFIIIC-110 Transcription Factor Binding
DNase1, Open Chromatin, DNase1 Hypersensitive Site
ZBTB7A, Transcription Factor, ZBTB7A Transcription Factor Binding

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	5.034	1
	5.034	1
(flanking)	4.156	0.998

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	145	wt: 0.43 / mu: 0.58	wt: TGCAGCCCCGCGTGG mu: TGCAGCCCCGCGTCG	CAGC\|cccg
Donor increased	157	wt: 0.33 / mu: 0.49	wt: TGGGGGGCGGCGCCC mu: TCGGGGGCGGCGCCC	GGGG\|gcgg

distance from splice site

123

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

mutated

not conserved

Ptroglodytes

all identical

ENSPTRG00000010198

Mmulatta

all identical

ENSMMUG00000003046

Fcatus

no alignment

ENSFCAG00000010765

n/a

Mmusculus

all identical

ENSMUSG00000020150

Ggallus

all identical

ENSGALG00000024304

Trubripes

all identical

ENSTRUG00000003251

Drerio

all identical

ENSDARG00000070844

Dmelanogaster

no homologue

Celegans

no homologue

Xtropicalis

all identical

ENSXETG00000003703

protein features

start (aa)	end (aa)	feature	details
13	236	DOMAIN	RMT2.	lost
17	20	HELIX		lost
20	20	BINDING	S-adenosyl-L-methionine.	lost
25	27	STRAND		might get lost (downstream of altered splice site)
31	36	STRAND		might get lost (downstream of altered splice site)
39	43	STRAND		might get lost (downstream of altered splice site)
42	42	BINDING	Substrate (By similarity).	might get lost (downstream of altered splice site)
44	46	HELIX		might get lost (downstream of altered splice site)
46	46	BINDING	Substrate (By similarity).	might get lost (downstream of altered splice site)
47	57	HELIX		might get lost (downstream of altered splice site)
50	50	BINDING	S-adenosyl-L-methionine.	might get lost (downstream of altered splice site)
58	60	TURN		might get lost (downstream of altered splice site)
62	67	STRAND		might get lost (downstream of altered splice site)
69	74	REGION	S-adenosyl-L-methionine binding.	might get lost (downstream of altered splice site)
73	78	HELIX		might get lost (downstream of altered splice site)
83	90	STRAND		might get lost (downstream of altered splice site)
90	92	REGION	S-adenosyl-L-methionine.	might get lost (downstream of altered splice site)
93	102	HELIX		might get lost (downstream of altered splice site)
103	105	HELIX		might get lost (downstream of altered splice site)
107	115	STRAND		might get lost (downstream of altered splice site)
117	118	REGION	S-adenosyl-L-methionine binding.	might get lost (downstream of altered splice site)
117	120	HELIX		might get lost (downstream of altered splice site)
121	123	HELIX		might get lost (downstream of altered splice site)
129	134	STRAND		might get lost (downstream of altered splice site)
135	135	BINDING	S-adenosyl-L-methionine and substrate (By similarity).	might get lost (downstream of altered splice site)
141	143	HELIX		might get lost (downstream of altered splice site)
144	146	TURN		might get lost (downstream of altered splice site)
147	154	HELIX		might get lost (downstream of altered splice site)
156	159	HELIX		might get lost (downstream of altered splice site)
160	168	STRAND		might get lost (downstream of altered splice site)
171	172	REGION	Substrate binding.	might get lost (downstream of altered splice site)
171	177	HELIX		might get lost (downstream of altered splice site)
178	181	TURN		might get lost (downstream of altered splice site)
185	192	HELIX		might get lost (downstream of altered splice site)
194	200	HELIX		might get lost (downstream of altered splice site)
204	206	HELIX		might get lost (downstream of altered splice site)
207	213	STRAND		might get lost (downstream of altered splice site)
222	222	MOD_RES	Phosphotyrosine.	might get lost (downstream of altered splice site)
223	223	MOD_RES	Phosphotyrosine.	might get lost (downstream of altered splice site)
226	234	STRAND		might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

711 / 711

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

237 / 237

position of stopcodon in wt / mu cDNA

778 / 778

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

68 / 68

chromosome

strand

-1

last intron/exon boundary

638

theoretical NMD boundary in CDS

520

length of CDS

711

coding sequence (CDS) position

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

126

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

153

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

1401417

original gDNA sequence snippet

CGAGAACTGCAGCCCCGCGTGGGGGGCGGCGCCCGCGGCCT

altered gDNA sequence snippet

CGAGAACTGCAGCCCCGCGTCGGGGGCGGCGCCCGCGGCCT

original cDNA sequence snippet

CGAGAACTGCAGCCCCGCGTGGGGGGCGGCGCCCGCGGCCT

altered cDNA sequence snippet

CGAGAACTGCAGCCCCGCGTCGGGGGCGGCGCCCGCGGCCT

wildtype AA sequence

MSAPSATPIF APGENCSPAW GAAPAAYDAA DTHLRILGKP VMERWETPYM HALAAAASSK
GGRVLEVGFG MAIAASKVQE APIDEHWIIE CNDGVFQRLR DWAPRQTHKV IPLKGLWEDV
APTLPDGHFD GILYDTYPLS EETWHTHQFN FIKNHAFRLL KPGGVLTYCN LTSWGELMKS
KYSDITIMFE ETQVPALLEA GFRRENIRTE VMALVPPADC RYYAFPQMIT PLVTKG*

mutated AA sequence

MSAPSATPIF APGENCSPAS GAAPAAYDAA DTHLRILGKP VMERWETPYM HALAAAASSK
GGRVLEVGFG MAIAASKVQE APIDEHWIIE CNDGVFQRLR DWAPRQTHKV IPLKGLWEDV
APTLPDGHFD GILYDTYPLS EETWHTHQFN FIKNHAFRLL KPGGVLTYCN LTSWGELMKS
KYSDITIMFE ETQVPALLEA GFRRENIRTE VMALVPPADC RYYAFPQMIT PLVTKG*

speed

0.98 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: 0.999999999999999 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CI1414351)
known disease mutation at this position (HGMD CM041007)
known disease mutation: rs8303 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr19:1401417C>GN/A show variant in all transcripts IGV

HGNC symbol

GAMT

Ensembl transcript ID

ENST00000447102

Genbank transcript ID

NM_138924

UniProt peptide

Q14353

alteration type

single base exchange

alteration region

CDS

DNA changes

c.59G>C
cDNA.153G>C
g.153G>C

AA changes

W20S Score: 177 explain score(s)

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

frameshift

known variant

regulatory features

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	5.034	1
	5.034	1
(flanking)	4.156	0.998

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	145	wt: 0.43 / mu: 0.58	wt: TGCAGCCCCGCGTGG mu: TGCAGCCCCGCGTCG	CAGC\|cccg
Donor increased	157	wt: 0.33 / mu: 0.49	wt: TGGGGGGCGGCGCCC mu: TCGGGGGCGGCGCCC	GGGG\|gcgg

distance from splice site

123

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

mutated

not conserved

Ptroglodytes

all identical

ENSPTRG00000010198

Mmulatta

all identical

ENSMMUG00000003046

Fcatus

no alignment

ENSFCAG00000010765

n/a

Mmusculus

all identical

ENSMUSG00000020150

Ggallus

all identical

ENSGALG00000024304

Trubripes

all identical

ENSTRUG00000003251

Drerio

all identical

ENSDARG00000070844

Dmelanogaster

no homologue

Celegans

no homologue

Xtropicalis

all identical

ENSXETG00000003703

protein features

start (aa)	end (aa)	feature	details
13	236	DOMAIN	RMT2.	lost
17	20	HELIX		lost
20	20	BINDING	S-adenosyl-L-methionine.	lost
25	27	STRAND		might get lost (downstream of altered splice site)
31	36	STRAND		might get lost (downstream of altered splice site)
39	43	STRAND		might get lost (downstream of altered splice site)
42	42	BINDING	Substrate (By similarity).	might get lost (downstream of altered splice site)
44	46	HELIX		might get lost (downstream of altered splice site)
46	46	BINDING	Substrate (By similarity).	might get lost (downstream of altered splice site)
47	57	HELIX		might get lost (downstream of altered splice site)
50	50	BINDING	S-adenosyl-L-methionine.	might get lost (downstream of altered splice site)
58	60	TURN		might get lost (downstream of altered splice site)
62	67	STRAND		might get lost (downstream of altered splice site)
69	74	REGION	S-adenosyl-L-methionine binding.	might get lost (downstream of altered splice site)
73	78	HELIX		might get lost (downstream of altered splice site)
83	90	STRAND		might get lost (downstream of altered splice site)
90	92	REGION	S-adenosyl-L-methionine.	might get lost (downstream of altered splice site)
93	102	HELIX		might get lost (downstream of altered splice site)
103	105	HELIX		might get lost (downstream of altered splice site)
107	115	STRAND		might get lost (downstream of altered splice site)
117	118	REGION	S-adenosyl-L-methionine binding.	might get lost (downstream of altered splice site)
117	120	HELIX		might get lost (downstream of altered splice site)
121	123	HELIX		might get lost (downstream of altered splice site)
129	134	STRAND		might get lost (downstream of altered splice site)
135	135	BINDING	S-adenosyl-L-methionine and substrate (By similarity).	might get lost (downstream of altered splice site)
141	143	HELIX		might get lost (downstream of altered splice site)
144	146	TURN		might get lost (downstream of altered splice site)
147	154	HELIX		might get lost (downstream of altered splice site)
156	159	HELIX		might get lost (downstream of altered splice site)
160	168	STRAND		might get lost (downstream of altered splice site)
171	172	REGION	Substrate binding.	might get lost (downstream of altered splice site)
171	177	HELIX		might get lost (downstream of altered splice site)
178	181	TURN		might get lost (downstream of altered splice site)
185	192	HELIX		might get lost (downstream of altered splice site)
194	200	HELIX		might get lost (downstream of altered splice site)
204	206	HELIX		might get lost (downstream of altered splice site)
207	213	STRAND		might get lost (downstream of altered splice site)
222	222	MOD_RES	Phosphotyrosine.	might get lost (downstream of altered splice site)
223	223	MOD_RES	Phosphotyrosine.	might get lost (downstream of altered splice site)
226	234	STRAND		might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

810 / 810

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

270 / 270

position of stopcodon in wt / mu cDNA

904 / 904

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

95 / 95

chromosome

strand

-1

last intron/exon boundary

554

theoretical NMD boundary in CDS

409

length of CDS

810

coding sequence (CDS) position

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

153

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

153

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

1401417

original gDNA sequence snippet

CGAGAACTGCAGCCCCGCGTGGGGGGCGGCGCCCGCGGCCT

altered gDNA sequence snippet

CGAGAACTGCAGCCCCGCGTCGGGGGCGGCGCCCGCGGCCT

original cDNA sequence snippet

CGAGAACTGCAGCCCCGCGTGGGGGGCGGCGCCCGCGGCCT

altered cDNA sequence snippet

CGAGAACTGCAGCCCCGCGTCGGGGGCGGCGCCCGCGGCCT

wildtype AA sequence

MSAPSATPIF APGENCSPAW GAAPAAYDAA DTHLRILGKP VMERWETPYM HALAAAASSK
GGRVLEVGFG MAIAASKVQE APIDEHWIIE CNDGVFQRLR DWAPRQTHKV IPLKGLWEDV
APTLPDGHFD GILYDTYPLS EETWHTHQFN FIKNHAFRLL KPGGVLTYCN LTSWGELMKS
KYSDITIMFE VRPPEVPHGS PGSDLGWGWE GAAGATLLPG EGPFLTPWVG WTVLVHLEIK
VLCLAQWLPG AVAQVYNPST VEGRGGQIA*

mutated AA sequence

MSAPSATPIF APGENCSPAS GAAPAAYDAA DTHLRILGKP VMERWETPYM HALAAAASSK
GGRVLEVGFG MAIAASKVQE APIDEHWIIE CNDGVFQRLR DWAPRQTHKV IPLKGLWEDV
APTLPDGHFD GILYDTYPLS EETWHTHQFN FIKNHAFRLL KPGGVLTYCN LTSWGELMKS
KYSDITIMFE VRPPEVPHGS PGSDLGWGWE GAAGATLLPG EGPFLTPWVG WTVLVHLEIK
VLCLAQWLPG AVAQVYNPST VEGRGGQIA*

speed

0.55 s

MutationTaster - study a chromosomal position

Results

Taster files

mutation t@sting

Prediction

disease causing

mutation t@sting

Prediction

disease causing

Problems