rs2994388
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000429.3(MAT1A):c.1085+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 1,613,602 control chromosomes in the GnomAD database, including 187,721 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.54 ( 23804 hom., cov: 32)
Exomes 𝑓: 0.47 ( 163917 hom. )
Consequence
MAT1A
NM_000429.3 intron
NM_000429.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.117
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 Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.95).
BP6
Variant 10-80274506-G-A is Benign according to our data. Variant chr10-80274506-G-A is described in ClinVar as [Benign]. Clinvar id is 256103.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-80274506-G-A is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAT1A | NM_000429.3 | c.1085+14C>T | intron_variant | ENST00000372213.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAT1A | ENST00000372213.8 | c.1085+14C>T | intron_variant | 1 | NM_000429.3 | P1 | |||
MAT1A | ENST00000480845.1 | n.317+14C>T | intron_variant, non_coding_transcript_variant | 3 | |||||
MAT1A | ENST00000485270.5 | n.597+14C>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.543 AC: 82509AN: 151952Hom.: 23765 Cov.: 32
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GnomAD3 exomes AF: 0.506 AC: 127090AN: 251288Hom.: 33272 AF XY: 0.505 AC XY: 68547AN XY: 135858
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GnomAD4 exome AF: 0.468 AC: 683826AN: 1461532Hom.: 163917 Cov.: 49 AF XY: 0.471 AC XY: 342566AN XY: 727082
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GnomAD4 genome AF: 0.543 AC: 82611AN: 152070Hom.: 23804 Cov.: 32 AF XY: 0.546 AC XY: 40551AN XY: 74336
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Hepatic methionine adenosyltransferase deficiency Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at