dbSNP rs4933327: MAT1A:c.1086-44C>T (chr10-80273927-G-A) – 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.1086-44C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,348,844 control chromosomes in the GnomAD database, including 33,040 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3277 hom., cov: 33)

Exomes 𝑓: 0.22 ( 29763 hom. )

Consequence

MAT1A
NM_000429.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.141

Publications

10 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=-0.82).

BP6

Variant 10-80273927-G-A is Benign according to our data. Variant chr10-80273927-G-A is described in ClinVar as Benign. ClinVar VariationId is 1223539.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT1A	NM_000429.3 link	c.1086-44C>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.1086-44C>T	intron_variant	Intron 8 of 8	1	NM_000429.3	ENSP00000361287.3	Q00266
MAT1A	ENST00000480845.1 link	n.318-44C>T	intron_variant	Intron 2 of 4	3
MAT1A	ENST00000485270.5 link	n.598-44C>T	intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29798

AN:

152106

Hom.:

3268

Cov.:

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.241

Gnomad AMR

AF:

0.205

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.433

Gnomad SAS

AF:

0.318

Gnomad FIN

AF:

0.229

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.210

Gnomad OTH

AF:

0.200

GnomAD2 exomes

AF:

0.234

AC:

58107

AN:

248682

AF XY:

0.238

show subpopulations

Gnomad AFR exome

AF:

0.119

Gnomad AMR exome

AF:

0.208

Gnomad ASJ exome

AF:

0.148

Gnomad EAS exome

AF:

0.440

Gnomad FIN exome

AF:

0.227

Gnomad NFE exome

AF:

0.216

Gnomad OTH exome

AF:

0.228

GnomAD4 exome

AF:

0.215

AC:

257632

AN:

1196620

Hom.:

29763

Cov.:

AF XY:

0.218

AC XY:

132649

AN XY:

608782

show subpopulations

African (AFR)

AF:

0.113

AC:

3080

AN:

27256

American (AMR)

AF:

0.212

AC:

9394

AN:

44342

Ashkenazi Jewish (ASJ)

AF:

0.141

AC:

3437

AN:

24454

East Asian (EAS)

AF:

0.383

AC:

14722

AN:

38432

South Asian (SAS)

AF:

0.296

AC:

23823

AN:

80370

European-Finnish (FIN)

AF:

0.226

AC:

12015

AN:

53234

Middle Eastern (MID)

AF:

0.237

AC:

1222

AN:

5158

European-Non Finnish (NFE)

AF:

0.205

AC:

178937

AN:

872066

Other (OTH)

AF:

0.214

AC:

11002

AN:

51308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

9216

18431

27647

36862

46078

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5576

11152

16728

22304

27880

<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:

0.196

AC:

29823

AN:

152224

Hom.:

3277

Cov.:

AF XY:

0.201

AC XY:

14973

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.121

AC:

5035

AN:

41546

American (AMR)

AF:

0.205

AC:

3141

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.132

AC:

459

AN:

3472

East Asian (EAS)

AF:

0.434

AC:

2243

AN:

5166

South Asian (SAS)

AF:

0.319

AC:

1537

AN:

4820

European-Finnish (FIN)

AF:

0.229

AC:

2429

AN:

10590

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.210

AC:

14283

AN:

68012

Other (OTH)

AF:

0.202

AC:

426

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1227

2454

3682

4909

6136

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

326

652

978

1304

1630

<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:

0.204

Hom.:

4484

Bravo

AF:

0.191

Asia WGS

AF:

0.356

AC:

1235

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

- -

Mar 03, 2015

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

-0.82

CADD

Benign

0.44

(source)

DANN

Benign

0.76

PhyloP100

-0.14

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