Genetic Variant MAT1A:c.91+111G>A (chr10-80289222-C-T) – ACMG Classification: Benign (-20 pts)

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.91+111G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.053 in 868,534 control chromosomes in the GnomAD database, including 1,436 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.062 ( 291 hom., cov: 32)

Exomes 𝑓: 0.051 ( 1145 hom. )

Consequence

MAT1A
NM_000429.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.195

Publications

3 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=-0.86).

BP6

Variant 10-80289222-C-T is Benign according to our data. Variant chr10-80289222-C-T is described in ClinVar as [Benign]. Clinvar id is 1280037.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.086 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT1A	NM_000429.3 link	c.91+111G>A		intron_variant	Intron 1 of 8	ENST00000372213.8	NP_000420.1	Q00266

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAT1A	ENST00000372213.8 link	c.91+111G>A		intron_variant	Intron 1 of 8	1	NM_000429.3	ENSP00000361287.3		Q00266
MAT1A	ENST00000455001.1 link	c.25+111G>A		intron_variant	Intron 1 of 4	5		ENSP00000414961.1		B1ANE6

Frequencies

GnomAD3 genomes

AF:

0.0619

AC:

9413

AN:

152088

Hom.:

290

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0883

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.0407

Gnomad ASJ

AF:

0.0899

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0400

Gnomad FIN

AF:

0.0617

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0558

Gnomad OTH

AF:

0.0468

GnomAD4 exome

AF:

0.0511

AC:

36620

AN:

716328

Hom.:

1145

AF XY:

0.0516

AC XY:

19808

AN XY:

384122

show subpopulations

African (AFR)

AF:

0.0912

AC:

1755

AN:

19248

American (AMR)

AF:

0.0239

AC:

1021

AN:

42654

Ashkenazi Jewish (ASJ)

AF:

0.0966

AC:

2060

AN:

21332

East Asian (EAS)

AF:

0.000165

AC:

AN:

36280

South Asian (SAS)

AF:

0.0446

AC:

3133

AN:

70306

European-Finnish (FIN)

AF:

0.0593

AC:

2802

AN:

47286

Middle Eastern (MID)

AF:

0.0488

AC:

210

AN:

4304

European-Non Finnish (NFE)

AF:

0.0541

AC:

23738

AN:

438944

Other (OTH)

AF:

0.0527

AC:

1895

AN:

35974

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1897

3794

5690

7587

9484

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0619

AC:

9414

AN:

152206

Hom.:

291

Cov.:

AF XY:

0.0619

AC XY:

4603

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.0884

AC:

3668

AN:

41514

American (AMR)

AF:

0.0405

AC:

620

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0899

AC:

312

AN:

3472

East Asian (EAS)

AF:

0.000771

AC:

AN:

5186

South Asian (SAS)

AF:

0.0390

AC:

188

AN:

4818

European-Finnish (FIN)

AF:

0.0617

AC:

653

AN:

10592

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0558

AC:

3797

AN:

68014

Other (OTH)

AF:

0.0459

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

452

904

1356

1808

2260

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0719

Hom.:

Bravo

AF:

0.0594

Asia WGS

AF:

0.0220

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

- -

May 14, 2021

GeneDx

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

-0.86

CADD

Benign

4.7

(source)

DANN

Benign

0.71

PhyloP100

0.20

PromoterAI

-0.040

Neutral

(source)

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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10-80289222-C-T

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