10-80275086-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -5.50

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 256107.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-80275086-A-G is described in Lovd as [Benign].

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT1A	NM_000429.3 link	c.882T>C	p.Ala294Ala	synonymous_variant	Exon 7 of 9	ENST00000372213.8	NP_000420.1	Q00266

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAT1A	ENST00000372213.8 link	c.882T>C	p.Ala294Ala	synonymous_variant	Exon 7 of 9	1	NM_000429.3	ENSP00000361287.3	Q00266
MAT1A	ENST00000480845.1 link	n.114T>C		non_coding_transcript_exon_variant	Exon 1 of 5	3
MAT1A	ENST00000485270.5 link	n.394T>C		non_coding_transcript_exon_variant	Exon 1 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.737

AC:

112004

AN:

151962

Hom.:

42406

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.721

AC:

151977

AN:

210926

Hom.:

56159

AF XY:

0.716

AC XY:

81462

AN XY:

113698

show subpopulations

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 SAS exome

AF:

0.818

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.:

AF XY:

0.670

AC XY:

477884

AN XY:

712864

show subpopulations

Gnomad4 AFR exome

AF:

0.900

Gnomad4 AMR exome

AF:

0.791

Gnomad4 ASJ exome

AF:

0.690

Gnomad4 EAS exome

AF:

0.946

Gnomad4 SAS exome

AF:

0.821

Gnomad4 FIN exome

AF:

0.670

Gnomad4 NFE exome

AF:

0.632

Gnomad4 OTH exome

AF:

0.701

GnomAD4 genome

AF:

0.737

AC:

112099

AN:

152080

Hom.:

42444

Cov.:

AF XY:

0.743

AC XY:

55233

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.891

Gnomad4 AMR

AF:

0.755

Gnomad4 ASJ

AF:

0.685

Gnomad4 EAS

AF:

0.966

Gnomad4 SAS

AF:

0.842

Gnomad4 FIN

AF:

0.674

Gnomad4 NFE

AF:

0.629

Gnomad4 OTH

AF:

0.732

Alfa

AF:

0.655

Hom.:

42973

Bravo

AF:

0.749

Asia WGS

AF:

0.878

AC:

3054

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Apr 21, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hepatic methionine adenosyltransferase deficiency

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.075

DANN

Benign

0.23

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over