10-80280296-A-G

Position:

chr10-80280296-A-G

Variant summary

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

The NM_000429.3(MAT1A):c.426T>C(p.Ala142=) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.585

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 256105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-80280296-A-G is described in Lovd as [Benign].

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAT1A	NM_000429.3 linkuse as main transcript	c.426T>C	p.Ala142=	synonymous_variant	5/9	ENST00000372213.8	NP_000420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAT1A	ENST00000372213.8 linkuse as main transcript	c.426T>C	p.Ala142=	synonymous_variant	5/9	1	NM_000429.3	ENSP00000361287	P1
MAT1A	ENST00000455001.1 linkuse as main transcript	c.237T>C	p.Ala79=	synonymous_variant	4/5	5		ENSP00000414961

Frequencies

GnomAD3 genomes

AF:

0.770

AC:

116921

AN:

151772

Hom.:

46259

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.756

AC:

190035

AN:

251342

Hom.:

73325

AF XY:

0.751

AC XY:

102030

AN XY:

135860

show subpopulations

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 SAS exome

AF:

0.836

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.:

AF XY:

0.702

AC XY:

510239

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.944

Gnomad4 AMR exome

AF:

0.814

Gnomad4 ASJ exome

AF:

0.755

Gnomad4 EAS exome

AF:

0.948

Gnomad4 SAS exome

AF:

0.835

Gnomad4 FIN exome

AF:

0.697

Gnomad4 NFE exome

AF:

0.665

Gnomad4 OTH exome

AF:

0.734

GnomAD4 genome

AF:

0.771

AC:

117040

AN:

151890

Hom.:

46318

Cov.:

AF XY:

0.775

AC XY:

57513

AN XY:

74196

show subpopulations

Gnomad4 AFR

AF:

0.936

Gnomad4 AMR

AF:

0.782

Gnomad4 ASJ

AF:

0.748

Gnomad4 EAS

AF:

0.967

Gnomad4 SAS

AF:

0.852

Gnomad4 FIN

AF:

0.697

Gnomad4 NFE

AF:

0.661

Gnomad4 OTH

AF:

0.766

Alfa

AF:

0.700

Hom.:

54605

Bravo

AF:

0.784

Asia WGS

AF:

0.891

AC:

3096

AN:

3478

EpiCase

AF:

0.673

EpiControl

AF:

0.670

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hepatic methionine adenosyltransferase deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

5.5

DANN

Benign

0.49

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