Genetic Variant MAT1A:c.*1599_*1600insTTCAGGCTGG (chr10-80272181-C-CCCAGCCTGAA) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000429.3(MAT1A):c.*1599_*1600insTTCAGGCTGG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.43 ( 14379 hom., cov: 0)

Exomes 𝑓: 0.31 ( 4 hom. )

Consequence

MAT1A
NM_000429.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.730

Publications

0 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 -10 ACMG points.

BP6

Variant 10-80272181-C-CCCAGCCTGAA is Benign according to our data. Variant chr10-80272181-C-CCCAGCCTGAA is described in ClinVar as [Benign]. Clinvar id is 301153.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT1A	NM_000429.3 link	c.1599_1600insTTCAGGCTGG		3_prime_UTR_variant	Exon 9 of 9	ENST00000372213.8	NP_000420.1	Q00266

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAT1A	ENST00000372213.8 link	c.1599_1600insTTCAGGCTGG	3_prime_UTR_variant	Exon 9 of 9	1	NM_000429.3	ENSP00000361287.3	Q00266
MAT1A	ENST00000485270.5 link	n.2299_2300insTTCAGGCTGG	non_coding_transcript_exon_variant	Exon 3 of 3	2
MAT1A	ENST00000480845.1 link	n.762-96_762-95insTTCAGGCTGG	intron_variant	Intron 4 of 4	3

Frequencies

GnomAD3 genomes

AF:

0.426

AC:

64591

AN:

151590

Hom.:

14336

Cov.:

show subpopulations

Gnomad AFR

AF:

0.517

Gnomad AMI

AF:

0.222

Gnomad AMR

AF:

0.475

Gnomad ASJ

AF:

0.392

Gnomad EAS

AF:

0.448

Gnomad SAS

AF:

0.593

Gnomad FIN

AF:

0.374

Gnomad MID

AF:

0.415

Gnomad NFE

AF:

0.359

Gnomad OTH

AF:

0.408

GnomAD4 exome

AF:

0.313

AC:

AN:

Hom.:

Cov.:

AF XY:

0.333

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.340

AC:

AN:

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.426

AC:

64692

AN:

151708

Hom.:

14379

Cov.:

AF XY:

0.432

AC XY:

32008

AN XY:

74108

show subpopulations

African (AFR)

AF:

0.518

AC:

21408

AN:

41362

American (AMR)

AF:

0.475

AC:

7245

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.392

AC:

1359

AN:

3466

East Asian (EAS)

AF:

0.450

AC:

2304

AN:

5122

South Asian (SAS)

AF:

0.593

AC:

2857

AN:

4814

European-Finnish (FIN)

AF:

0.374

AC:

3954

AN:

10568

Middle Eastern (MID)

AF:

0.432

AC:

127

AN:

294

European-Non Finnish (NFE)

AF:

0.359

AC:

24368

AN:

67816

Other (OTH)

AF:

0.411

AC:

868

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1822

3643

5465

7286

9108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.240

Hom.:

435

Asia WGS

AF:

0.545

AC:

1897

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hepatic methionine adenosyltransferase deficiency

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.73

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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10-80272181-C-CCCAGCCTGAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over