rs1985908

chr10-80272484-A-Gchr10-80272484-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000429.3(MAT1A):c.*1297T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,072 control chromosomes in the GnomAD database, including 10,751 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.36 (10749 hom., cov: 31)
  • Exomes 𝑓: 0.26 (2 hom.)
• Consequence: MAT1A NM_000429.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.175

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 10-80272484-A-G is Benign according to our data. Variant chr10-80272484-A-G is described in ClinVar as [Benign]. Clinvar id is 301155.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAT1A	NM_000429.3	c.*1297T>C		3_prime_UTR_variant	9/9	ENST00000372213.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAT1A	ENST00000372213.8	c.*1297T>C		3_prime_UTR_variant	9/9	1	NM_000429.3	P1
MAT1A	ENST00000480845.1	n.717T>C		non_coding_transcript_exon_variant	4/5	3
MAT1A	ENST00000485270.5	n.1997T>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.356 AC: 53998 AN: 151852 Hom.: 10737 Cov.: 31

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.947

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.361

GnomAD4 exome AF: 0.265 AC: 27 AN: 102 Hom.: 2 Cov.: 0 AF XY: 0.250 AC XY: 19 AN XY: 76

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.238

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.356 AC: 54051 AN: 151970 Hom.: 10749 Cov.: 31 AF XY: 0.366 AC XY: 27196 AN XY: 74278

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.947

Gnomad4 SAS AF: 0.466

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.364

Alfa AF: 0.326 Hom.: 17497

Bravo AF: 0.354

Asia WGS AF: 0.648 AC: 2247 AN: 3478

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

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.7
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: rs1985908; hg19: chr10-82032240;