10-80275098-T-C

Variant names:

• chr10-80275098-T-C
• rs10788546
• NM_000429.3:c.870A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000429.3(MAT1A):​c.870A>G​(p.Val290Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 1,602,276 control chromosomes in the GnomAD database, including 372,274 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (42467 hom., cov: 32)
  • Exomes 𝑓: 0.67 (329807 hom.)
• Consequence: MAT1A NM_000429.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 1.49
• Publications: 27 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: AR, AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 10-80275098-T-C is Benign according to our data. Variant chr10-80275098-T-C is described in ClinVar as Benign. ClinVar VariationId is 256106.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.49 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000429.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAT1A	NM_000429.3	MANE Select	c.870A>G	p.Val290Val	synonymous	Exon 7 of 9	NP_000420.1	Q00266

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAT1A	ENST00000372213.8	TSL:1 MANE Select	c.870A>G	p.Val290Val	synonymous	Exon 7 of 9	ENSP00000361287.3	Q00266
	MAT1A	ENST00000871627.1		c.870A>G	p.Val290Val	synonymous	Exon 7 of 9	ENSP00000541686.1
	MAT1A	ENST00000871624.1		c.1035A>G	p.Val345Val	synonymous	Exon 7 of 9	ENSP00000541683.1

Frequencies

GnomAD3 genomes AF: 0.737 AC: 112050 AN: 152006 Hom.: 42429 Cov.: 32

Gnomad AFR AF: 0.892

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.966

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.729

GnomAD2 exomes AF: 0.726 AC: 167059 AN: 230202 AF XY: 0.721

Gnomad AFR exome AF: 0.893

Gnomad AMR exome AF: 0.797

Gnomad ASJ exome AF: 0.687

Gnomad EAS exome AF: 0.975

Gnomad FIN exome AF: 0.671

Gnomad NFE exome AF: 0.628

Gnomad OTH exome AF: 0.700

GnomAD4 exome AF: 0.669 AC: 970252 AN: 1450152 Hom.: 329807 Cov.: 51 AF XY: 0.671 AC XY: 483647 AN XY: 720252

African (AFR) AF: 0.900 AC: 29883 AN: 33218

American (AMR) AF: 0.794 AC: 34262 AN: 43170

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 17861 AN: 25890

East Asian (EAS) AF: 0.947 AC: 37155 AN: 39222

South Asian (SAS) AF: 0.823 AC: 69534 AN: 84442

European-Finnish (FIN) AF: 0.671 AC: 35111 AN: 52338

Middle Eastern (MID) AF: 0.769 AC: 4325 AN: 5624

European-Non Finnish (NFE) AF: 0.633 AC: 700131 AN: 1106330

Other (OTH) AF: 0.701 AC: 41990 AN: 59918

GnomAD4 genome AF: 0.737 AC: 112146 AN: 152124 Hom.: 42467 Cov.: 32 AF XY: 0.743 AC XY: 55269 AN XY: 74366

African (AFR) AF: 0.891 AC: 37021 AN: 41538

American (AMR) AF: 0.755 AC: 11551 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2377 AN: 3472

East Asian (EAS) AF: 0.966 AC: 4995 AN: 5172

South Asian (SAS) AF: 0.844 AC: 4077 AN: 4828

European-Finnish (FIN) AF: 0.675 AC: 7137 AN: 10574

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.629 AC: 42715 AN: 67932

Other (OTH) AF: 0.732 AC: 1545 AN: 2112

Alfa AF: 0.662 Hom.: 49361

Bravo AF: 0.749

Asia WGS AF: 0.878 AC: 3054 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Hepatic methionine adenosyltransferase deficiency (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	7.4
DANN	Benign	0.84
PhyloP100		1.5
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: rs10788546; hg19: chr10-82034854; COSMIC: COSV108217325; COSMIC: COSV108217325;