rs2236569

Variant names:

• chr10-80283820-G-A
• rs2236569
• NM_000429.3:c.292+96C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-80283820-G-A
• chr10-80283820-G-C
• chr10-80283820-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.292+96C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 1,561,168 control chromosomes in the GnomAD database, including 395,853 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (46275 hom., cov: 34)
  • Exomes 𝑓: 0.70 (349578 hom.)
• Consequence: MAT1A NM_000429.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.620
• Publications: 13 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 10-80283820-G-A is Benign according to our data. Variant chr10-80283820-G-A is described in ClinVar as Benign. ClinVar VariationId is 1229238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT1A	NM_000429.3	c.292+96C>T		intron_variant	Intron 3 of 8	ENST00000372213.8	NP_000420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAT1A	ENST00000372213.8	c.292+96C>T		intron_variant	Intron 3 of 8	1	NM_000429.3	ENSP00000361287.3
MAT1A	ENST00000455001.1	c.103+1692C>T		intron_variant	Intron 2 of 4	5		ENSP00000414961.1

Frequencies

GnomAD3 genomes AF: 0.769 AC: 117017 AN: 152108 Hom.: 46216 Cov.: 34

Gnomad AFR AF: 0.936

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.851

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.764

GnomAD4 exome AF: 0.700 AC: 985749 AN: 1408942 Hom.: 349578 AF XY: 0.702 AC XY: 493596 AN XY: 703578

African (AFR) AF: 0.943 AC: 30563 AN: 32404

American (AMR) AF: 0.813 AC: 36302 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 19492 AN: 25798

East Asian (EAS) AF: 0.928 AC: 36597 AN: 39422

South Asian (SAS) AF: 0.834 AC: 70904 AN: 85004

European-Finnish (FIN) AF: 0.697 AC: 36817 AN: 52798

Middle Eastern (MID) AF: 0.809 AC: 3278 AN: 4054

European-Non Finnish (NFE) AF: 0.665 AC: 708884 AN: 1066318

Other (OTH) AF: 0.733 AC: 42912 AN: 58518

GnomAD4 genome AF: 0.769 AC: 117136 AN: 152226 Hom.: 46275 Cov.: 34 AF XY: 0.774 AC XY: 57594 AN XY: 74422

African (AFR) AF: 0.936 AC: 38875 AN: 41544

American (AMR) AF: 0.783 AC: 11977 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.748 AC: 2598 AN: 3472

East Asian (EAS) AF: 0.939 AC: 4854 AN: 5168

South Asian (SAS) AF: 0.850 AC: 4100 AN: 4822

European-Finnish (FIN) AF: 0.697 AC: 7386 AN: 10596

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.661 AC: 44948 AN: 68010

Other (OTH) AF: 0.767 AC: 1618 AN: 2110

Alfa AF: 0.702 Hom.: 48177

Bravo AF: 0.783

Asia WGS AF: 0.880 AC: 3060 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.15
DANN	Benign	0.39
PhyloP100		-0.62
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: rs2236569; hg19: chr10-82043576;