rs1143694

Variant names:

• chr10-80280296-A-G
• rs1143694
• NM_000429.3:c.426T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-80280296-A-G
• chr10-80280296-A-C
• chr10-80280296-A-T

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.426T>C​(p.Ala142Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 1,613,670 control chromosomes in the GnomAD database, including 409,105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (46318 hom., cov: 30)
  • Exomes 𝑓: 0.70 (362787 hom.)
• Consequence: MAT1A NM_000429.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.585
• Publications: 24 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=-0.58).
• BP6: Variant 10-80280296-A-G is Benign according to our data. Variant chr10-80280296-A-G is described in ClinVar as Benign. ClinVar VariationId is 256105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.585 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 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.426T>C	p.Ala142Ala	synonymous	Exon 5 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.426T>C	p.Ala142Ala	synonymous	Exon 5 of 9	ENSP00000361287.3	Q00266
	MAT1A	ENST00000871627.1		c.426T>C	p.Ala142Ala	synonymous	Exon 5 of 9	ENSP00000541686.1
	MAT1A	ENST00000871624.1		c.591T>C	p.Ala197Ala	synonymous	Exon 5 of 9	ENSP00000541683.1

Frequencies

GnomAD3 genomes AF: 0.770 AC: 116921 AN: 151772 Hom.: 46259 Cov.: 30

Gnomad AFR AF: 0.936

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.968

Gnomad SAS AF: 0.853

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.764

GnomAD2 exomes AF: 0.756 AC: 190035 AN: 251342 AF XY: 0.751

Gnomad AFR exome AF: 0.936

Gnomad AMR exome AF: 0.816

Gnomad ASJ exome AF: 0.756

Gnomad EAS exome AF: 0.975

Gnomad FIN exome AF: 0.699

Gnomad NFE exome AF: 0.667

Gnomad OTH exome AF: 0.734

GnomAD4 exome AF: 0.700 AC: 1022897 AN: 1461780 Hom.: 362787 Cov.: 63 AF XY: 0.702 AC XY: 510239 AN XY: 727178

African (AFR) AF: 0.944 AC: 31593 AN: 33480

American (AMR) AF: 0.814 AC: 36383 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 19736 AN: 26136

East Asian (EAS) AF: 0.948 AC: 37631 AN: 39700

South Asian (SAS) AF: 0.835 AC: 72051 AN: 86256

European-Finnish (FIN) AF: 0.697 AC: 37215 AN: 53372

Middle Eastern (MID) AF: 0.820 AC: 4731 AN: 5766

European-Non Finnish (NFE) AF: 0.665 AC: 739203 AN: 1111956

Other (OTH) AF: 0.734 AC: 44354 AN: 60390

GnomAD4 genome AF: 0.771 AC: 117040 AN: 151890 Hom.: 46318 Cov.: 30 AF XY: 0.775 AC XY: 57513 AN XY: 74196

African (AFR) AF: 0.936 AC: 38794 AN: 41446

American (AMR) AF: 0.782 AC: 11952 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.748 AC: 2598 AN: 3472

East Asian (EAS) AF: 0.967 AC: 4967 AN: 5134

South Asian (SAS) AF: 0.852 AC: 4080 AN: 4786

European-Finnish (FIN) AF: 0.697 AC: 7340 AN: 10538

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.661 AC: 44909 AN: 67926

Other (OTH) AF: 0.766 AC: 1614 AN: 2106

Alfa AF: 0.711 Hom.: 77576

Bravo AF: 0.784

Asia WGS AF: 0.891 AC: 3096 AN: 3478

EpiCase AF: 0.673

EpiControl AF: 0.670

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	Hepatic methionine adenosyltransferase deficiency (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	5.5
DANN	Benign	0.49
PhyloP100		0.58
Mutation Taster		=98/2	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: rs1143694; hg19: chr10-82040052; COSMIC: COSV64746096; COSMIC: COSV64746096;