10-80280846-A-G

Position:

• chr10-80280846-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000372213.8(MAT1A):​c.293-54T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0755 in 1,296,188 control chromosomes in the GnomAD database, including 4,316 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.055 (293 hom., cov: 32)
  • Exomes 𝑓: 0.078 (4023 hom.)
• Consequence: MAT1A ENST00000372213.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.459

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 10-80280846-A-G is Benign according to our data. Variant chr10-80280846-A-G is described in ClinVar as [Benign]. Clinvar id is 1287609.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAT1A	NM_000429.3	c.293-54T>C		intron_variant		ENST00000372213.8	NP_000420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAT1A	ENST00000372213.8	c.293-54T>C		intron_variant		1	NM_000429.3	ENSP00000361287	P1
MAT1A	ENST00000455001.1	c.104-54T>C		intron_variant		5		ENSP00000414961

Frequencies

GnomAD3 genomes AF: 0.0546 AC: 8306 AN: 152158 Hom.: 293 Cov.: 32

Gnomad AFR AF: 0.0151

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.0475

Gnomad ASJ AF: 0.0772

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0510

Gnomad FIN AF: 0.0489

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0832

Gnomad OTH AF: 0.0645

GnomAD4 exome AF: 0.0783 AC: 89569 AN: 1143912 Hom.: 4023 AF XY: 0.0780 AC XY: 45606 AN XY: 584546

Gnomad4 AFR exome AF: 0.0141

Gnomad4 AMR exome AF: 0.0383

Gnomad4 ASJ exome AF: 0.0802

Gnomad4 EAS exome AF: 0.000157

Gnomad4 SAS exome AF: 0.0571

Gnomad4 FIN exome AF: 0.0550

Gnomad4 NFE exome AF: 0.0900

Gnomad4 OTH exome AF: 0.0707

GnomAD4 genome AF: 0.0545 AC: 8303 AN: 152276 Hom.: 293 Cov.: 32 AF XY: 0.0525 AC XY: 3908 AN XY: 74454

Gnomad4 AFR AF: 0.0150

Gnomad4 AMR AF: 0.0473

Gnomad4 ASJ AF: 0.0772

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0512

Gnomad4 FIN AF: 0.0489

Gnomad4 NFE AF: 0.0832

Gnomad4 OTH AF: 0.0639

Alfa AF: 0.0631 Hom.: 37

Bravo AF: 0.0545

Asia WGS AF: 0.0220 AC: 75 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.90
DANN	Benign	0.37

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: rs71481597; hg19: chr10-82040602;