10-80275086-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

26 publications found

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 Gene-Disease associations (from GenCC):

methionine adenosyltransferase deficiency
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, G2P, Orphanet

MAT1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

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

GnomAD2 exomes

AF:

0.721

AC:

151977

AN:

210926

AF XY:

0.716

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 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

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

17886

35772

53658

71544

89430

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18824

37648

56472

75296

94120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.737

AC:

112099

AN:

152080

Hom.:

42444

Cov.:

AF XY:

0.743

AC XY:

55233

AN XY:

74336

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1458

2916

4375

5833

7291

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

834

1668

2502

3336

4170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.665

Hom.:

65375

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

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

- -

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

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.075

(source)

DANN

Benign

0.23

PhyloP100

-5.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over