rs4933327

Positions:

• chr10-80273927-G-A
• chr10-80273927-G-C

Variant summary

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

The NM_000429.3(MAT1A):​c.1086-44C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,348,844 control chromosomes in the GnomAD database, including 33,040 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3277 hom., cov: 33)
  • Exomes 𝑓: 0.22 (29763 hom.)
• Consequence: MAT1A NM_000429.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.141

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=-0.82).
• BP6: Variant 10-80273927-G-A is Benign according to our data. Variant chr10-80273927-G-A is described in ClinVar as [Benign]. Clinvar id is 1223539.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAT1A	NM_000429.3	c.1086-44C>T		intron_variant		ENST00000372213.8	NP_000420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAT1A	ENST00000372213.8	c.1086-44C>T		intron_variant		1	NM_000429.3	ENSP00000361287	P1
MAT1A	ENST00000480845.1	n.318-44C>T		intron_variant, non_coding_transcript_variant		3
MAT1A	ENST00000485270.5	n.598-44C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29798 AN: 152106 Hom.: 3268 Cov.: 33

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.200

GnomAD3 exomes AF: 0.234 AC: 58107 AN: 248682 Hom.: 7537 AF XY: 0.238 AC XY: 32004 AN XY: 134646

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.208

Gnomad ASJ exome AF: 0.148

Gnomad EAS exome AF: 0.440

Gnomad SAS exome AF: 0.297

Gnomad FIN exome AF: 0.227

Gnomad NFE exome AF: 0.216

Gnomad OTH exome AF: 0.228

GnomAD4 exome AF: 0.215 AC: 257632 AN: 1196620 Hom.: 29763 Cov.: 17 AF XY: 0.218 AC XY: 132649 AN XY: 608782

Gnomad4 AFR exome AF: 0.113

Gnomad4 AMR exome AF: 0.212

Gnomad4 ASJ exome AF: 0.141

Gnomad4 EAS exome AF: 0.383

Gnomad4 SAS exome AF: 0.296

Gnomad4 FIN exome AF: 0.226

Gnomad4 NFE exome AF: 0.205

Gnomad4 OTH exome AF: 0.214

GnomAD4 genome AF: 0.196 AC: 29823 AN: 152224 Hom.: 3277 Cov.: 33 AF XY: 0.201 AC XY: 14973 AN XY: 74408

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.202

Alfa AF: 0.207 Hom.: 3620

Bravo AF: 0.191

Asia WGS AF: 0.356 AC: 1235 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	-0.82
CADD	Benign	0.44
DANN	Benign	0.76

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: rs4933327; hg19: chr10-82033683; COSMIC: COSV64745789; COSMIC: COSV64745789;