rs2282367

Positions:

• chr10-80280590-A-G
• chr10-80280590-A-T

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.405+90T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 1,209,720 control chromosomes in the GnomAD database, including 316,580 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.77 (46373 hom., cov: 30)
  • Exomes 𝑓: 0.71 (270207 hom.)
• Consequence: MAT1A NM_000429.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.604

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 10-80280590-A-G is Benign according to our data. Variant chr10-80280590-A-G is described in ClinVar as [Benign]. Clinvar id is 1222995.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAT1A	NM_000429.3	c.405+90T>C		intron_variant		ENST00000372213.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAT1A	ENST00000372213.8	c.405+90T>C		intron_variant		1	NM_000429.3	P1
MAT1A	ENST00000455001.1	c.216+90T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.770 AC: 117046 AN: 151924 Hom.: 46314 Cov.: 30

Gnomad AFR AF: 0.936

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.968

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.787

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.765

GnomAD4 exome AF: 0.709 AC: 749931 AN: 1057678 Hom.: 270207 AF XY: 0.711 AC XY: 387025 AN XY: 544314

Gnomad4 AFR exome AF: 0.940

Gnomad4 AMR exome AF: 0.814

Gnomad4 ASJ exome AF: 0.754

Gnomad4 EAS exome AF: 0.947

Gnomad4 SAS exome AF: 0.836

Gnomad4 FIN exome AF: 0.697

Gnomad4 NFE exome AF: 0.666

Gnomad4 OTH exome AF: 0.737

GnomAD4 genome AF: 0.771 AC: 117165 AN: 152042 Hom.: 46373 Cov.: 30 AF XY: 0.775 AC XY: 57612 AN XY: 74326

Gnomad4 AFR AF: 0.936

Gnomad4 AMR AF: 0.783

Gnomad4 ASJ AF: 0.749

Gnomad4 EAS AF: 0.968

Gnomad4 SAS AF: 0.851

Gnomad4 FIN AF: 0.697

Gnomad4 NFE AF: 0.661

Gnomad4 OTH AF: 0.767

Alfa AF: 0.689 Hom.: 74715

Bravo AF: 0.784

Asia WGS AF: 0.890 AC: 3095 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.49

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: rs2282367; hg19: chr10-82040346;