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
• Publications: 15 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: AR, AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P, ClinGen

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 VariationId is 256103.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000429.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAT1A	NM_000429.3	MANE Select	c.1085+14C>T		intron	N/A	NP_000420.1	Q00266

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAT1A	ENST00000372213.8	TSL:1 MANE Select	c.1085+14C>T		intron	N/A	ENSP00000361287.3	Q00266
	MAT1A	ENST00000871627.1		c.1301+14C>T		intron	N/A	ENSP00000541686.1
	MAT1A	ENST00000871624.1		c.1250+14C>T		intron	N/A	ENSP00000541683.1

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

African (AFR) AF: 0.759 AC: 25422 AN: 33474

American (AMR) AF: 0.548 AC: 24487 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 12445 AN: 26122

East Asian (EAS) AF: 0.408 AC: 16183 AN: 39690

South Asian (SAS) AF: 0.625 AC: 53947 AN: 86250

European-Finnish (FIN) AF: 0.429 AC: 22888 AN: 53372

Middle Eastern (MID) AF: 0.555 AC: 3199 AN: 5768

European-Non Finnish (NFE) AF: 0.446 AC: 495706 AN: 1111750

Other (OTH) 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

African (AFR) AF: 0.747 AC: 30991 AN: 41488

American (AMR) AF: 0.543 AC: 8297 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1632 AN: 3470

East Asian (EAS) AF: 0.453 AC: 2334 AN: 5152

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

European-Finnish (FIN) AF: 0.424 AC: 4484 AN: 10574

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

European-Non Finnish (NFE) AF: 0.444 AC: 30205 AN: 67970

Other (OTH) AF: 0.519 AC: 1094 AN: 2108

Alfa AF: 0.485 Hom.: 53507

Bravo AF: 0.556

Asia WGS AF: 0.573 AC: 1995 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Hepatic methionine adenosyltransferase deficiency (2)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.13
DANN	Benign	0.52
PhyloP100		-0.12
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

Other links and lift over

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