rs2236568

Variant names:

• chr10-80276167-C-A
• rs2236568
• NM_000429.3:c.768+209G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000429.3(MAT1A):​c.768+209G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 151,978 control chromosomes in the GnomAD database, including 24,511 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.55 (24511 hom., cov: 32)
• Consequence: MAT1A NM_000429.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.764
• Publications: 6 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 10-80276167-C-A is Benign according to our data. Variant chr10-80276167-C-A is described in ClinVar as Benign. ClinVar VariationId is 1257538.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT1A	NM_000429.3	c.768+209G>T		intron_variant	Intron 6 of 8	ENST00000372213.8	NP_000420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAT1A	ENST00000372213.8	c.768+209G>T		intron_variant	Intron 6 of 8	1	NM_000429.3	ENSP00000361287.3

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83400 AN: 151858 Hom.: 24468 Cov.: 32

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.521

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.549 AC: 83506 AN: 151978 Hom.: 24511 Cov.: 32 AF XY: 0.551 AC XY: 40974 AN XY: 74298

African (AFR) AF: 0.769 AC: 31873 AN: 41456

American (AMR) AF: 0.545 AC: 8316 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1632 AN: 3472

East Asian (EAS) AF: 0.452 AC: 2336 AN: 5164

South Asian (SAS) AF: 0.646 AC: 3115 AN: 4820

European-Finnish (FIN) AF: 0.424 AC: 4480 AN: 10554

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30192 AN: 67938

Other (OTH) AF: 0.524 AC: 1103 AN: 2106

Alfa AF: 0.517 Hom.: 2756

Bravo AF: 0.564

Asia WGS AF: 0.576 AC: 2004 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 22, 2019

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	-0.91
CADD	Benign	0.29
DANN	Benign	0.48
PhyloP100		-0.76
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2236568; hg19: chr10-82035923; COSMIC: COSV107465414; COSMIC: COSV107465414;