chr10-80273838-G-A

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.1131C>T(p.Tyr377Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 1,610,836 control chromosomes in the GnomAD database, including 187,594 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 23794 hom., cov: 32)

Exomes 𝑓: 0.47 ( 163800 hom. )

Consequence

MAT1A
NM_000429.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.471

Publications

34 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=-0.73).

BP6

Variant 10-80273838-G-A is Benign according to our data. Variant chr10-80273838-G-A is described in ClinVar as Benign. ClinVar VariationId is 256104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.471 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT1A	NM_000429.3 link	c.1131C>T	p.Tyr377Tyr	synonymous_variant	Exon 9 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.1131C>T	p.Tyr377Tyr	synonymous_variant	Exon 9 of 9	1	NM_000429.3	ENSP00000361287.3	Q00266
MAT1A	ENST00000480845.1 link	n.363C>T		non_coding_transcript_exon_variant	Exon 3 of 5	3
MAT1A	ENST00000485270.5 link	n.643C>T		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.543

AC:

82513

AN:

151940

Hom.:

23755

Cov.:

show subpopulations

Gnomad AFR

AF:

0.747

Gnomad AMI

AF:

0.347

Gnomad AMR

AF:

0.543

Gnomad ASJ

AF:

0.470

Gnomad EAS

AF:

0.453

Gnomad SAS

AF:

0.645

Gnomad FIN

AF:

0.424

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.444

Gnomad OTH

AF:

0.517

GnomAD2 exomes

AF:

0.506

AC:

126549

AN:

250074

AF XY:

0.505

show subpopulations

Gnomad AFR exome

AF:

0.752

Gnomad AMR exome

AF:

0.544

Gnomad ASJ exome

AF:

0.479

Gnomad EAS exome

AF:

0.455

Gnomad FIN exome

AF:

0.429

Gnomad NFE exome

AF:

0.453

Gnomad OTH exome

AF:

0.496

GnomAD4 exome

AF:

0.468

AC:

682324

AN:

1458778

Hom.:

163800

Cov.:

AF XY:

0.471

AC XY:

341894

AN XY:

725856

show subpopulations

African (AFR)

AF:

0.759

AC:

25345

AN:

33414

American (AMR)

AF:

0.548

AC:

24501

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.476

AC:

12435

AN:

26112

East Asian (EAS)

AF:

0.408

AC:

16177

AN:

39682

South Asian (SAS)

AF:

0.626

AC:

53922

AN:

86198

European-Finnish (FIN)

AF:

0.429

AC:

22913

AN:

53416

Middle Eastern (MID)

AF:

0.554

AC:

3184

AN:

5744

European-Non Finnish (NFE)

AF:

0.446

AC:

494377

AN:

1109250

Other (OTH)

AF:

0.489

AC:

29470

AN:

60250

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

18692

37384

56076

74768

93460

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15176

30352

45528

60704

75880

<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:

0.543

AC:

82615

AN:

152058

Hom.:

23794

Cov.:

AF XY:

0.545

AC XY:

40539

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.747

AC:

30995

AN:

41510

American (AMR)

AF:

0.543

AC:

8301

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.470

AC:

1632

AN:

3472

East Asian (EAS)

AF:

0.454

AC:

2335

AN:

5146

South Asian (SAS)

AF:

0.646

AC:

3113

AN:

4816

European-Finnish (FIN)

AF:

0.424

AC:

4486

AN:

10570

Middle Eastern (MID)

AF:

0.493

AC:

145

AN:

294

European-Non Finnish (NFE)

AF:

0.444

AC:

30195

AN:

67940

Other (OTH)

AF:

0.519

AC:

1098

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1819

3638

5458

7277

9096

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

706

1412

2118

2824

3530

<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:

0.481

Hom.:

63527

Bravo

AF:

0.556

Asia WGS

AF:

0.573

AC:

1995

AN:

3478

EpiCase

AF:

0.455

EpiControl

AF:

0.447

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

-0.73

CADD

Benign

0.26

(source)

DANN

Benign

0.33

PhyloP100

-0.47

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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