rs118204006
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PP3_ModeratePP5
The NM_000429.3(MAT1A):c.1006G>A(p.Gly336Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Consequence
MAT1A
NM_000429.3 missense
NM_000429.3 missense
Scores
16
2
1
Clinical Significance
Conservation
PhyloP100: 7.55
Genes affected
MAT1A (HGNC:6903): (methionine adenosyltransferase 1A) This gene catalyzes a two-step reaction that involves the transfer of the adenosyl moiety of ATP to methionine to form S-adenosylmethionine and tripolyphosphate, which is subsequently cleaved to PPi and Pi. S-adenosylmethionine is the source of methyl groups for most biological methylations. The encoded protein is found as a homotetramer (MAT I) or a homodimer (MAT III) whereas a third form, MAT II (gamma), is encoded by the MAT2A gene. Mutations in this gene are associated with methionine adenosyltransferase deficiency. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
?
Variant 10-80274599-C-T is Pathogenic according to our data. Variant chr10-80274599-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 1211.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAT1A | NM_000429.3 | c.1006G>A | p.Gly336Arg | missense_variant | 8/9 | ENST00000372213.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAT1A | ENST00000372213.8 | c.1006G>A | p.Gly336Arg | missense_variant | 8/9 | 1 | NM_000429.3 | P1 | |
MAT1A | ENST00000480845.1 | n.238G>A | non_coding_transcript_exon_variant | 2/5 | 3 | ||||
MAT1A | ENST00000485270.5 | n.518G>A | non_coding_transcript_exon_variant | 2/3 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251470Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135914
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GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461884Hom.: 0 Cov.: 34 AF XY: 0.00000963 AC XY: 7AN XY: 727242
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ExAC
?
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2
Asia WGS
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1
AN:
3478
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hepatic methionine adenosyltransferase deficiency Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 01, 2000 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Pathogenic
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
A;A
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Loss of ubiquitination at K340 (P = 0.0528);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at