10-80272785-TG-T

Position:

• chr10-80272785-TG-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000429.3(MAT1A):​c.*995del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.099 in 152,310 control chromosomes in the GnomAD database, including 998 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.099 (998 hom., cov: 31)
  • Exomes 𝑓: 0.036 (0 hom.)
• Consequence: MAT1A NM_000429.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.955

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 -10 ACMG points.

• BP6: Variant 10-80272785-TG-T is Benign according to our data. Variant chr10-80272785-TG-T is described in ClinVar as [Benign]. Clinvar id is 301164.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAT1A	NM_000429.3	c.*995del		3_prime_UTR_variant	9/9	ENST00000372213.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAT1A	ENST00000372213.8	c.*995del		3_prime_UTR_variant	9/9	1	NM_000429.3	P1
MAT1A	ENST00000485270.5	n.1695del		non_coding_transcript_exon_variant	3/3	2
MAT1A	ENST00000480845.1	n.621-206del		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0990 AC: 15050 AN: 152084 Hom.: 989 Cov.: 31

Gnomad AFR AF: 0.0304

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0174

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.0720

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.112

GnomAD4 exome AF: 0.0364 AC: 4 AN: 110 Hom.: 0 Cov.: 0 AF XY: 0.0455 AC XY: 4 AN XY: 88

Gnomad4 AFR exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0444

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0990 AC: 15074 AN: 152200 Hom.: 998 Cov.: 31 AF XY: 0.100 AC XY: 7458 AN XY: 74414

Gnomad4 AFR AF: 0.0303

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.0174

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.0720

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.116

Alfa AF: 0.0476 Hom.: 48

Bravo AF: 0.102

Asia WGS AF: 0.145 AC: 505 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hepatic methionine adenosyltransferase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs5786439; hg19: chr10-82032541;