chr10-80285164-G-T

Variant names:

• chr10-80285164-G-T
• rs7081756
• NM_000429.3:c.169+348C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

MAT1A Gene-Disease associations (from GenCC):

• methionine adenosyltransferase deficiency

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MAT1A	NM_000429.3	c.169+348C>A		intron_variant	Intron 2 of 8	ENST00000372213.8	NP_000420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAT1A	ENST00000372213.8	c.169+348C>A		intron_variant	Intron 2 of 8	1	NM_000429.3	ENSP00000361287.3
MAT1A	ENST00000455001.1	c.103+348C>A		intron_variant	Intron 2 of 4	5		ENSP00000414961.1

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

African (AFR) AF: 0.719 AC: 29790 AN: 41440

American (AMR) AF: 0.605 AC: 9239 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2392 AN: 3470

East Asian (EAS) AF: 0.0707 AC: 366 AN: 5174

South Asian (SAS) AF: 0.487 AC: 2338 AN: 4800

European-Finnish (FIN) AF: 0.506 AC: 5336 AN: 10550

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.646 AC: 43881 AN: 67966

Other (OTH) AF: 0.619 AC: 1304 AN: 2108

Alfa AF: 0.642 Hom.: 104693

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
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7081756; hg19: chr10-82044920;