rs72809554

Positions:

• chr10-80274406-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000372213.8(MAT1A):​c.1085+114G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0291 in 1,457,376 control chromosomes in the GnomAD database, including 750 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.024 (52 hom., cov: 33)
  • Exomes 𝑓: 0.030 (698 hom.)
• Consequence: MAT1A ENST00000372213.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.125

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0244 (3712/152282) while in subpopulation NFE AF= 0.0326 (2219/68030). AF 95% confidence interval is 0.0315. There are 52 homozygotes in gnomad4. There are 1761 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 52 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAT1A	NM_000429.3	c.1085+114G>A		intron_variant		ENST00000372213.8	NP_000420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAT1A	ENST00000372213.8	c.1085+114G>A		intron_variant		1	NM_000429.3	ENSP00000361287	P1
MAT1A	ENST00000480845.1	n.317+114G>A		intron_variant, non_coding_transcript_variant		3
MAT1A	ENST00000485270.5	n.597+114G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0244 AC: 3713 AN: 152164 Hom.: 52 Cov.: 33

Gnomad AFR AF: 0.0121

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0247

Gnomad ASJ AF: 0.0634

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.00684

Gnomad FIN AF: 0.0221

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0326

Gnomad OTH AF: 0.0292

GnomAD4 exome AF: 0.0296 AC: 38672 AN: 1305094 Hom.: 698 AF XY: 0.0291 AC XY: 19133 AN XY: 656706

Gnomad4 AFR exome AF: 0.0118

Gnomad4 AMR exome AF: 0.0161

Gnomad4 ASJ exome AF: 0.0646

Gnomad4 EAS exome AF: 0.000261

Gnomad4 SAS exome AF: 0.0113

Gnomad4 FIN exome AF: 0.0251

Gnomad4 NFE exome AF: 0.0325

Gnomad4 OTH exome AF: 0.0325

GnomAD4 genome AF: 0.0244 AC: 3712 AN: 152282 Hom.: 52 Cov.: 33 AF XY: 0.0236 AC XY: 1761 AN XY: 74462

Gnomad4 AFR AF: 0.0121

Gnomad4 AMR AF: 0.0246

Gnomad4 ASJ AF: 0.0634

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.00684

Gnomad4 FIN AF: 0.0221

Gnomad4 NFE AF: 0.0326

Gnomad4 OTH AF: 0.0289

Alfa AF: 0.0288 Hom.: 5

Bravo AF: 0.0243

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.41

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: rs72809554; hg19: chr10-82034162;