rs10887711

Variant names:

• chr10-80275086-A-G
• rs10887711
• NM_000429.3:c.882T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-80275086-A-G
• chr10-80275086-A-C
• chr10-80275086-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.882T>C​(p.Ala294Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 1,589,642 control chromosomes in the GnomAD database, including 368,288 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (42444 hom., cov: 33)
  • Exomes 𝑓: 0.67 (325844 hom.)
• Consequence: MAT1A NM_000429.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -5.50
• Publications: 26 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=-0.99).
• BP6: Variant 10-80275086-A-G is Benign according to our data. Variant chr10-80275086-A-G is described in ClinVar as Benign. ClinVar VariationId is 256107.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.5 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.882T>C	p.Ala294Ala	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.882T>C	p.Ala294Ala	synonymous	Exon 7 of 9	ENSP00000361287.3	Q00266
	MAT1A	ENST00000871627.1		c.882T>C	p.Ala294Ala	synonymous	Exon 7 of 9	ENSP00000541686.1
	MAT1A	ENST00000871624.1		c.1047T>C	p.Ala349Ala	synonymous	Exon 7 of 9	ENSP00000541683.1

Frequencies

GnomAD3 genomes AF: 0.737 AC: 112004 AN: 151962 Hom.: 42406 Cov.: 33

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: 0.842

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.729

GnomAD2 exomes AF: 0.721 AC: 151977 AN: 210926 AF XY: 0.716

Gnomad AFR exome AF: 0.890

Gnomad AMR exome AF: 0.793

Gnomad ASJ exome AF: 0.685

Gnomad EAS exome AF: 0.974

Gnomad FIN exome AF: 0.667

Gnomad NFE exome AF: 0.620

Gnomad OTH exome AF: 0.699

GnomAD4 exome AF: 0.668 AC: 960283 AN: 1437562 Hom.: 325844 Cov.: 55 AF XY: 0.670 AC XY: 477884 AN XY: 712864

African (AFR) AF: 0.900 AC: 29567 AN: 32868

American (AMR) AF: 0.791 AC: 32487 AN: 41082

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 17685 AN: 25644

East Asian (EAS) AF: 0.946 AC: 36235 AN: 38288

South Asian (SAS) AF: 0.821 AC: 68078 AN: 82910

European-Finnish (FIN) AF: 0.670 AC: 34553 AN: 51586

Middle Eastern (MID) AF: 0.767 AC: 4161 AN: 5428

European-Non Finnish (NFE) AF: 0.632 AC: 695825 AN: 1100248

Other (OTH) AF: 0.701 AC: 41692 AN: 59508

GnomAD4 genome AF: 0.737 AC: 112099 AN: 152080 Hom.: 42444 Cov.: 33 AF XY: 0.743 AC XY: 55233 AN XY: 74336

African (AFR) AF: 0.891 AC: 37007 AN: 41514

American (AMR) AF: 0.755 AC: 11548 AN: 15288

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

East Asian (EAS) AF: 0.966 AC: 4991 AN: 5168

South Asian (SAS) AF: 0.842 AC: 4063 AN: 4826

European-Finnish (FIN) AF: 0.674 AC: 7126 AN: 10566

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

European-Non Finnish (NFE) AF: 0.629 AC: 42713 AN: 67928

Other (OTH) AF: 0.732 AC: 1546 AN: 2112

Alfa AF: 0.665 Hom.: 65375

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	-0.99
CADD	Benign	0.075
DANN	Benign	0.23
PhyloP100		-5.5
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: rs10887711; hg19: chr10-82034842; COSMIC: COSV108217324; COSMIC: COSV108217324;