10-80272181-C-CCCAGCCTGAA

Variant summary

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

The NM_000429.3(MAT1A):c.*1599_*1600insTTCAGGCTGG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.43 (14379 hom., cov: 0)
  • Exomes 𝑓: 0.31 (4 hom.)
• Consequence: MAT1A NM_000429.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.730

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 10-80272181-C-CCCAGCCTGAA is Benign according to our data. Variant chr10-80272181-C-CCCAGCCTGAA is described in ClinVar as [Benign]. Clinvar id is 301153.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAT1A	NM_000429.3	c.*1599_*1600insTTCAGGCTGG		3_prime_UTR_variant	9/9	ENST00000372213.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAT1A	ENST00000372213.8	c.*1599_*1600insTTCAGGCTGG		3_prime_UTR_variant	9/9	1	NM_000429.3	P1
MAT1A	ENST00000485270.5	n.2299_2300insTTCAGGCTGG		non_coding_transcript_exon_variant	3/3	2
MAT1A	ENST00000480845.1	n.762-96_762-95insTTCAGGCTGG		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64591 AN: 151590 Hom.: 14336 Cov.: 0

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.408

GnomAD4 exome AF: 0.313 AC: 20 AN: 64 Hom.: 4 Cov.: 0 AF XY: 0.333 AC XY: 16 AN XY: 48

Gnomad4 AFR exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.340

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.426 AC: 64692 AN: 151708 Hom.: 14379 Cov.: 0 AF XY: 0.432 AC XY: 32008 AN XY: 74108

Gnomad4 AFR AF: 0.518

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.450

Gnomad4 SAS AF: 0.593

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.411

Alfa AF: 0.240 Hom.: 435

Asia WGS AF: 0.545 AC: 1897 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

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs145159688; hg19: chr10-82031937;