dbSNP rs72809554: MAT1A:c.1085+114G>A (chr10-80274406-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000429.3(MAT1A):c.1085+114G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0291 in 1,457,376 control chromosomes in the GnomAD database, including 750 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.024 ( 52 hom., cov: 33)

Exomes 𝑓: 0.030 ( 698 hom. )

Consequence

MAT1A
NM_000429.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.125

Publications

2 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0244 (3712/152282) while in subpopulation NFE AF = 0.0326 (2219/68030). AF 95% confidence interval is 0.0315. There are 52 homozygotes in GnomAd4. There are 1761 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 52 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT1A	NM_000429.3 link	c.1085+114G>A		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+114G>A	intron_variant	Intron 8 of 8	1	NM_000429.3	ENSP00000361287.3	Q00266
MAT1A	ENST00000480845.1 link	n.317+114G>A	intron_variant	Intron 2 of 4	3
MAT1A	ENST00000485270.5 link	n.597+114G>A	intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.0244

AC:

3713

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0121

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.0247

Gnomad ASJ

AF:

0.0634

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.00684

Gnomad FIN

AF:

0.0221

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0326

Gnomad OTH

AF:

0.0292

GnomAD4 exome

AF:

0.0296

AC:

38672

AN:

1305094

Hom.:

698

AF XY:

0.0291

AC XY:

19133

AN XY:

656706

show subpopulations

African (AFR)

AF:

0.0118

AC:

353

AN:

29982

American (AMR)

AF:

0.0161

AC:

711

AN:

44182

Ashkenazi Jewish (ASJ)

AF:

0.0646

AC:

1610

AN:

24910

East Asian (EAS)

AF:

0.000261

AC:

AN:

38352

South Asian (SAS)

AF:

0.0113

AC:

929

AN:

82226

European-Finnish (FIN)

AF:

0.0251

AC:

1186

AN:

47338

Middle Eastern (MID)

AF:

0.0488

AC:

264

AN:

5412

European-Non Finnish (NFE)

AF:

0.0325

AC:

31825

AN:

977762

Other (OTH)

AF:

0.0325

AC:

1784

AN:

54930

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

1980

3959

5939

7918

9898

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1138

2276

3414

4552

5690

<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:

0.0244

AC:

3712

AN:

152282

Hom.:

Cov.:

AF XY:

0.0236

AC XY:

1761

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0121

AC:

502

AN:

41552

American (AMR)

AF:

0.0246

AC:

377

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0634

AC:

220

AN:

3472

East Asian (EAS)

AF:

0.00135

AC:

AN:

5170

South Asian (SAS)

AF:

0.00684

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0221

AC:

235

AN:

10616

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0326

AC:

2219

AN:

68030

Other (OTH)

AF:

0.0289

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

192

384

575

767

959

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<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:

0.0288

Hom.:

Bravo

AF:

0.0243

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.6

(source)

DANN

Benign

0.41

PhyloP100

0.13

Mutation Taster

=100/0

polymorphism

(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

Computational scores

Splicing

Publications

Other links and lift over