rs2282367

Variant names:

• chr10-80280590-A-G
• rs2282367
• NM_000429.3:c.405+90T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-80280590-A-G
• chr10-80280590-A-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.405+90T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 1,209,720 control chromosomes in the GnomAD database, including 316,580 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (46373 hom., cov: 30)
  • Exomes 𝑓: 0.71 (270207 hom.)
• Consequence: MAT1A NM_000429.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.604
• Publications: 20 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=-0.92).
• BP6: Variant 10-80280590-A-G is Benign according to our data. Variant chr10-80280590-A-G is described in ClinVar as Benign. ClinVar VariationId is 1222995.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAT1A	NM_000429.3	MANE Select	c.405+90T>C		intron	N/A	NP_000420.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAT1A	ENST00000372213.8	TSL:1 MANE Select	c.405+90T>C		intron	N/A	ENSP00000361287.3
	MAT1A	ENST00000871627.1		c.405+90T>C		intron	N/A	ENSP00000541686.1
	MAT1A	ENST00000871624.1		c.405+90T>C		intron	N/A	ENSP00000541683.1

Frequencies

GnomAD3 genomes AF: 0.770 AC: 117046 AN: 151924 Hom.: 46314 Cov.: 30

Gnomad AFR AF: 0.936

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.968

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.787

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.765

GnomAD4 exome AF: 0.709 AC: 749931 AN: 1057678 Hom.: 270207 AF XY: 0.711 AC XY: 387025 AN XY: 544314

African (AFR) AF: 0.940 AC: 24171 AN: 25712

American (AMR) AF: 0.814 AC: 35983 AN: 44194

Ashkenazi Jewish (ASJ) AF: 0.754 AC: 17858 AN: 23696

East Asian (EAS) AF: 0.947 AC: 35863 AN: 37872

South Asian (SAS) AF: 0.836 AC: 65427 AN: 78278

European-Finnish (FIN) AF: 0.697 AC: 36504 AN: 52348

Middle Eastern (MID) AF: 0.822 AC: 4117 AN: 5006

European-Non Finnish (NFE) AF: 0.666 AC: 495294 AN: 743486

Other (OTH) AF: 0.737 AC: 34714 AN: 47086

GnomAD4 genome AF: 0.771 AC: 117165 AN: 152042 Hom.: 46373 Cov.: 30 AF XY: 0.775 AC XY: 57612 AN XY: 74326

African (AFR) AF: 0.936 AC: 38849 AN: 41510

American (AMR) AF: 0.783 AC: 11950 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 2597 AN: 3468

East Asian (EAS) AF: 0.968 AC: 4980 AN: 5146

South Asian (SAS) AF: 0.851 AC: 4098 AN: 4814

European-Finnish (FIN) AF: 0.697 AC: 7371 AN: 10582

Middle Eastern (MID) AF: 0.791 AC: 231 AN: 292

European-Non Finnish (NFE) AF: 0.661 AC: 44917 AN: 67946

Other (OTH) AF: 0.767 AC: 1617 AN: 2108

Alfa AF: 0.705 Hom.: 120748

Bravo AF: 0.784

Asia WGS AF: 0.890 AC: 3095 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.49
PhyloP100		-0.60
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: rs2282367; hg19: chr10-82040346;