rs2994388

Variant names:

• chr10-80274506-G-A
• rs2994388
• NM_000429.3:c.1085+14C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-80274506-G-A
• chr10-80274506-G-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.1085+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 1,613,602 control chromosomes in the GnomAD database, including 187,721 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (23804 hom., cov: 32)
  • Exomes 𝑓: 0.47 (163917 hom.)
• Consequence: MAT1A NM_000429.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.117

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 10-80274506-G-A is Benign according to our data. Variant chr10-80274506-G-A is described in ClinVar as [Benign]. Clinvar id is 256103.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-80274506-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT1A	NM_000429.3	c.1085+14C>T		intron_variant	Intron 8 of 8	ENST00000372213.8	NP_000420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAT1A	ENST00000372213.8	c.1085+14C>T		intron_variant	Intron 8 of 8	1	NM_000429.3	ENSP00000361287.3
MAT1A	ENST00000480845.1	n.317+14C>T		intron_variant	Intron 2 of 4	3
MAT1A	ENST00000485270.5	n.597+14C>T		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82509 AN: 151952 Hom.: 23765 Cov.: 32

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.516

GnomAD2 exomes AF: 0.506 AC: 127090 AN: 251288 AF XY: 0.505

Gnomad AFR exome AF: 0.753

Gnomad AMR exome AF: 0.544

Gnomad ASJ exome AF: 0.479

Gnomad EAS exome AF: 0.455

Gnomad FIN exome AF: 0.430

Gnomad NFE exome AF: 0.453

Gnomad OTH exome AF: 0.496

GnomAD4 exome AF: 0.468 AC: 683826 AN: 1461532 Hom.: 163917 Cov.: 49 AF XY: 0.471 AC XY: 342566 AN XY: 727082

Gnomad4 AFR exome AF: 0.759 AC: 25422 AN: 33474

Gnomad4 AMR exome AF: 0.548 AC: 24487 AN: 44722

Gnomad4 ASJ exome AF: 0.476 AC: 12445 AN: 26122

Gnomad4 EAS exome AF: 0.408 AC: 16183 AN: 39690

Gnomad4 SAS exome AF: 0.625 AC: 53947 AN: 86250

Gnomad4 FIN exome AF: 0.429 AC: 22888 AN: 53372

Gnomad4 NFE exome AF: 0.446 AC: 495706 AN: 1111750

Gnomad4 Remaining exome AF: 0.489 AC: 29549 AN: 60384

GnomAD4 genome AF: 0.543 AC: 82611 AN: 152070 Hom.: 23804 Cov.: 32 AF XY: 0.546 AC XY: 40551 AN XY: 74336

Gnomad4 AFR AF: 0.747 AC: 0.746987 AN: 0.746987

Gnomad4 AMR AF: 0.543 AC: 0.542784 AN: 0.542784

Gnomad4 ASJ AF: 0.470 AC: 0.470317 AN: 0.470317

Gnomad4 EAS AF: 0.453 AC: 0.453028 AN: 0.453028

Gnomad4 SAS AF: 0.646 AC: 0.646266 AN: 0.646266

Gnomad4 FIN AF: 0.424 AC: 0.424059 AN: 0.424059

Gnomad4 NFE AF: 0.444 AC: 0.444387 AN: 0.444387

Gnomad4 OTH AF: 0.519 AC: 0.518975 AN: 0.518975

Alfa AF: 0.485 Hom.: 53507

Bravo AF: 0.556

Asia WGS AF: 0.573 AC: 1995 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

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

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hepatic methionine adenosyltransferase deficiency Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

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	-0.95
CADD	Benign	0.13
DANN	Benign	0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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

Publications

LitVar

Other links and lift over

dbSNP: rs2994388; hg19: chr10-82034262; COSMIC: COSV64745501; COSMIC: COSV64745501;