rs2236569

chr10-80283820-G-Achr10-80283820-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000429.3(MAT1A):c.292+96C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 1,561,168 control chromosomes in the GnomAD database, including 395,853 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.77 (46275 hom., cov: 34)
  • Exomes 𝑓: 0.70 (349578 hom.)
• Consequence: MAT1A NM_000429.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.620

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 10-80283820-G-A is Benign according to our data. Variant chr10-80283820-G-A is described in ClinVar as [Benign]. Clinvar id is 1229238.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAT1A	NM_000429.3	c.292+96C>T		intron_variant		ENST00000372213.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAT1A	ENST00000372213.8	c.292+96C>T		intron_variant		1	NM_000429.3	P1
MAT1A	ENST00000455001.1	c.103+1692C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.769 AC: 117017 AN: 152108 Hom.: 46216 Cov.: 34

Gnomad AFR AF: 0.936

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.851

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.764

GnomAD4 exome AF: 0.700 AC: 985749 AN: 1408942 Hom.: 349578 AF XY: 0.702 AC XY: 493596 AN XY: 703578

Gnomad4 AFR exome AF: 0.943

Gnomad4 AMR exome AF: 0.813

Gnomad4 ASJ exome AF: 0.756

Gnomad4 EAS exome AF: 0.928

Gnomad4 SAS exome AF: 0.834

Gnomad4 FIN exome AF: 0.697

Gnomad4 NFE exome AF: 0.665

Gnomad4 OTH exome AF: 0.733

GnomAD4 genome AF: 0.769 AC: 117136 AN: 152226 Hom.: 46275 Cov.: 34 AF XY: 0.774 AC XY: 57594 AN XY: 74422

Gnomad4 AFR AF: 0.936

Gnomad4 AMR AF: 0.783

Gnomad4 ASJ AF: 0.748

Gnomad4 EAS AF: 0.939

Gnomad4 SAS AF: 0.850

Gnomad4 FIN AF: 0.697

Gnomad4 NFE AF: 0.661

Gnomad4 OTH AF: 0.767

Alfa AF: 0.690 Hom.: 35363

Bravo AF: 0.783

Asia WGS AF: 0.880 AC: 3060 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.15
Dann	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2236569; hg19: chr10-82043576;