NM_000429.3:c.91+916C>G

Variant names:

• chr10-80288417-G-C
• rs9421467
• NM_000429.3:c.91+916C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000429.3(MAT1A):​c.91+916C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0621 in 152,256 control chromosomes in the GnomAD database, including 292 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 0.062 (292 hom., cov: 32)
• Consequence: MAT1A NM_000429.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.239
• Publications: 2 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT1A	NM_000429.3	c.91+916C>G		intron_variant	Intron 1 of 8	ENST00000372213.8	NP_000420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAT1A	ENST00000372213.8	c.91+916C>G		intron_variant	Intron 1 of 8	1	NM_000429.3	ENSP00000361287.3
MAT1A	ENST00000455001.1	c.25+916C>G		intron_variant	Intron 1 of 4	5		ENSP00000414961.1

Frequencies

GnomAD3 genomes AF: 0.0621 AC: 9454 AN: 152138 Hom.: 291 Cov.: 32

Gnomad AFR AF: 0.0890

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0415

Gnomad ASJ AF: 0.0899

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0402

Gnomad FIN AF: 0.0609

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0558

Gnomad OTH AF: 0.0473

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

GnomAD4 genome AF: 0.0621 AC: 9455 AN: 152256 Hom.: 292 Cov.: 32 AF XY: 0.0621 AC XY: 4625 AN XY: 74444

African (AFR) AF: 0.0891 AC: 3701 AN: 41526

American (AMR) AF: 0.0414 AC: 633 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0899 AC: 312 AN: 3470

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5184

South Asian (SAS) AF: 0.0392 AC: 189 AN: 4826

European-Finnish (FIN) AF: 0.0609 AC: 646 AN: 10610

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0558 AC: 3796 AN: 68018

Other (OTH) AF: 0.0464 AC: 98 AN: 2114

Alfa AF: 0.0397 Hom.: 30

Bravo AF: 0.0599

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.5
DANN	Benign	0.71
PhyloP100		0.24
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: rs9421467; hg19: chr10-82048173;