10-80274506-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000429.3(MAT1A):c.1085+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 1,613,602 control chromosomes in the GnomAD database, including 187,721 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 23804 hom., cov: 32)

Exomes 𝑓: 0.47 ( 163917 hom. )

Consequence

MAT1A
NM_000429.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.117

Publications

15 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 10-80274506-G-A is Benign according to our data. Variant chr10-80274506-G-A is described in ClinVar as [Benign]. Clinvar id is 256103.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.1085+14C>T		intron_variant	Intron 8 of 8	ENST00000372213.8	NP_000420.1	Q00266

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAT1A	ENST00000372213.8 link	c.1085+14C>T	intron_variant	Intron 8 of 8	1	NM_000429.3	ENSP00000361287.3	Q00266
MAT1A	ENST00000480845.1 link	n.317+14C>T	intron_variant	Intron 2 of 4	3
MAT1A	ENST00000485270.5 link	n.597+14C>T	intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.543

AC:

82509

AN:

151952

Hom.:

23765

Cov.:

show subpopulations

Gnomad AFR

AF:

0.747

Gnomad AMI

AF:

0.345

Gnomad AMR

AF:

0.542

Gnomad ASJ

AF:

0.470

Gnomad EAS

AF:

0.452

Gnomad SAS

AF:

0.645

Gnomad FIN

AF:

0.424

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.444

Gnomad OTH

AF:

0.516

GnomAD2 exomes

AF:

0.506

AC:

127090

AN:

251288

AF XY:

0.505

show subpopulations

Gnomad AFR exome

AF:

0.753

Gnomad AMR exome

AF:

0.544

Gnomad ASJ exome

AF:

0.479

Gnomad EAS exome

AF:

0.455

Gnomad FIN exome

AF:

0.430

Gnomad NFE exome

AF:

0.453

Gnomad OTH exome

AF:

0.496

GnomAD4 exome

AF:

0.468

AC:

683826

AN:

1461532

Hom.:

163917

Cov.:

AF XY:

0.471

AC XY:

342566

AN XY:

727082

show subpopulations

African (AFR)

AF:

0.759

AC:

25422

AN:

33474

American (AMR)

AF:

0.548

AC:

24487

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.476

AC:

12445

AN:

26122

East Asian (EAS)

AF:

0.408

AC:

16183

AN:

39690

South Asian (SAS)

AF:

0.625

AC:

53947

AN:

86250

European-Finnish (FIN)

AF:

0.429

AC:

22888

AN:

53372

Middle Eastern (MID)

AF:

0.555

AC:

3199

AN:

5768

European-Non Finnish (NFE)

AF:

0.446

AC:

495706

AN:

1111750

Other (OTH)

AF:

0.489

AC:

29549

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

22009

44017

66026

88034

110043

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.543

AC:

82611

AN:

152070

Hom.:

23804

Cov.:

AF XY:

0.546

AC XY:

40551

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.747

AC:

30991

AN:

41488

American (AMR)

AF:

0.543

AC:

8297

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.470

AC:

1632

AN:

3470

East Asian (EAS)

AF:

0.453

AC:

2334

AN:

5152

South Asian (SAS)

AF:

0.646

AC:

3115

AN:

4820

European-Finnish (FIN)

AF:

0.424

AC:

4484

AN:

10574

Middle Eastern (MID)

AF:

0.497

AC:

146

AN:

294

European-Non Finnish (NFE)

AF:

0.444

AC:

30205

AN:

67970

Other (OTH)

AF:

0.519

AC:

1094

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1815

3629

5444

7258

9073

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.485

Hom.:

53507

Bravo

AF:

0.556

Asia WGS

AF:

0.573

AC:

1995

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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. -

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

-0.95

CADD

Benign

0.13

(source)

DANN

Benign

0.52

PhyloP100

-0.12

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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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10-80274506-G-A

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