rs71481596

Variant names:

• chr10-80280406-C-T
• rs71481596
• NM_000429.3:c.406-90G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-80280406-C-T
• chr10-80280406-C-A
• chr10-80280406-C-G

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.406-90G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0777 in 1,522,744 control chromosomes in the GnomAD database, including 5,171 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.054 (293 hom., cov: 31)
  • Exomes 𝑓: 0.080 (4878 hom.)
• Consequence: MAT1A NM_000429.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.266
• Publications: 3 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: Ambry Genetics, ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 10-80280406-C-T is Benign according to our data. Variant chr10-80280406-C-T is described in ClinVar as Benign. ClinVar VariationId is 1231953.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0813 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.406-90G>A		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.406-90G>A		intron	N/A	ENSP00000361287.3	Q00266
	MAT1A	ENST00000871624.1		c.481G>A	p.Val161Met	missense	Exon 5 of 9	ENSP00000541683.1
	MAT1A	ENST00000871626.1		c.439G>A	p.Val147Met	missense	Exon 5 of 9	ENSP00000541685.1

Frequencies

GnomAD3 genomes AF: 0.0545 AC: 8290 AN: 151994 Hom.: 293 Cov.: 31

Gnomad AFR AF: 0.0150

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.0475

Gnomad ASJ AF: 0.0772

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0505

Gnomad FIN AF: 0.0489

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0831

Gnomad OTH AF: 0.0642

GnomAD4 exome AF: 0.0803 AC: 110016 AN: 1370632 Hom.: 4878 AF XY: 0.0798 AC XY: 54671 AN XY: 685454

African (AFR) AF: 0.0138 AC: 436 AN: 31598

American (AMR) AF: 0.0386 AC: 1641 AN: 42514

Ashkenazi Jewish (ASJ) AF: 0.0801 AC: 2036 AN: 25418

East Asian (EAS) AF: 0.000207 AC: 8 AN: 38616

South Asian (SAS) AF: 0.0568 AC: 4723 AN: 83204

European-Finnish (FIN) AF: 0.0560 AC: 2549 AN: 45492

Middle Eastern (MID) AF: 0.0967 AC: 491 AN: 5076

European-Non Finnish (NFE) AF: 0.0903 AC: 94025 AN: 1041264

Other (OTH) AF: 0.0715 AC: 4107 AN: 57450

GnomAD4 genome AF: 0.0545 AC: 8287 AN: 152112 Hom.: 293 Cov.: 31 AF XY: 0.0525 AC XY: 3902 AN XY: 74340

African (AFR) AF: 0.0150 AC: 622 AN: 41492

American (AMR) AF: 0.0474 AC: 724 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0772 AC: 268 AN: 3470

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5168

South Asian (SAS) AF: 0.0508 AC: 244 AN: 4806

European-Finnish (FIN) AF: 0.0489 AC: 518 AN: 10586

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0831 AC: 5648 AN: 67988

Other (OTH) AF: 0.0636 AC: 134 AN: 2108

Alfa AF: 0.0272 Hom.: 15

Bravo AF: 0.0544

Asia WGS AF: 0.0220 AC: 75 AN: 3478

ClinVar

ClinVar submissions

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	-0.88
CADD	Benign	2.5
DANN	Benign	0.50
PhyloP100		-0.27
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: rs71481596; hg19: chr10-82040162;