rs7081756

Positions:

• chr10-80285164-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000429.3(MAT1A):​c.169+348C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 151,988 control chromosomes in the GnomAD database, including 31,221 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.63 (31221 hom., cov: 32)
• Consequence: MAT1A NM_000429.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAT1A	NM_000429.3	c.169+348C>A		intron_variant		ENST00000372213.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAT1A	ENST00000372213.8	c.169+348C>A		intron_variant		1	NM_000429.3	P1
MAT1A	ENST00000455001.1	c.103+348C>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95327 AN: 151872 Hom.: 31160 Cov.: 32

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.0706

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.621

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.628 AC: 95442 AN: 151988 Hom.: 31221 Cov.: 32 AF XY: 0.617 AC XY: 45852 AN XY: 74304

Gnomad4 AFR AF: 0.719

Gnomad4 AMR AF: 0.605

Gnomad4 ASJ AF: 0.689

Gnomad4 EAS AF: 0.0707

Gnomad4 SAS AF: 0.487

Gnomad4 FIN AF: 0.506

Gnomad4 NFE AF: 0.646

Gnomad4 OTH AF: 0.619

Alfa AF: 0.643 Hom.: 44443

Bravo AF: 0.639

Asia WGS AF: 0.343 AC: 1196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.12
DANN	Benign	0.41

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: rs7081756; hg19: chr10-82044920;