chr10-80272575-C-T

Variant names:

• chr10-80272575-C-T
• rs1832683
• NM_000429.3:c.*1206G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000429.3(MAT1A):​c.*1206G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,390 control chromosomes in the GnomAD database, including 3,501 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3499 hom., cov: 32)
  • Exomes 𝑓: 0.14 (2 hom.)
• Consequence: MAT1A NM_000429.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.32
• Publications: 11 publications found

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]

MAT1A Gene-Disease associations (from GenCC):

• methionine adenosyltransferase deficiency

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 10-80272575-C-T is Benign according to our data. Variant chr10-80272575-C-T is described in ClinVar as [Benign]. Clinvar id is 301158.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT1A	NM_000429.3	c.*1206G>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000372213.8	NP_000420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAT1A	ENST00000372213.8	c.*1206G>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_000429.3	ENSP00000361287.3
MAT1A	ENST00000480845.1	n.626G>A		non_coding_transcript_exon_variant	Exon 4 of 5	3
MAT1A	ENST00000485270.5	n.1906G>A		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31274 AN: 151962 Hom.: 3482 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.0183

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.216

GnomAD4 exome AF: 0.139 AC: 43 AN: 310 Hom.: 2 Cov.: 0 AF XY: 0.136 AC XY: 31 AN XY: 228

African (AFR) AF: 0.125 AC: 2 AN: 16

American (AMR) AF: 0.250 AC: 1 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 2 AN: 6

East Asian (EAS) AF: 0.00 AC: 0 AN: 6

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.133 AC: 4 AN: 30

Middle Eastern (MID) AF: 0.250 AC: 1 AN: 4

European-Non Finnish (NFE) AF: 0.135 AC: 31 AN: 230

Other (OTH) AF: 0.143 AC: 2 AN: 14

GnomAD4 genome AF: 0.206 AC: 31326 AN: 152080 Hom.: 3499 Cov.: 32 AF XY: 0.205 AC XY: 15252 AN XY: 74346

African (AFR) AF: 0.260 AC: 10782 AN: 41422

American (AMR) AF: 0.269 AC: 4108 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 862 AN: 3472

East Asian (EAS) AF: 0.0184 AC: 95 AN: 5176

South Asian (SAS) AF: 0.288 AC: 1389 AN: 4824

European-Finnish (FIN) AF: 0.134 AC: 1419 AN: 10602

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12100 AN: 67990

Other (OTH) AF: 0.218 AC: 461 AN: 2114

Alfa AF: 0.187 Hom.: 10458

Bravo AF: 0.215

Asia WGS AF: 0.182 AC: 636 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Hepatic methionine adenosyltransferase deficiency Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.82
CADD	Benign	11
DANN	Benign	0.41
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.27		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.27		Position offset: 5

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

Other links and lift over

dbSNP: rs1832683; hg19: chr10-82032331;