NM_000429.3(MAT1A):c.839G>T (p.Gly280Val) AND Hepatic methionine adenosyltransferase deficiency

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 16, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003636765.2

Allele description [Variation Report for NM_000429.3(MAT1A):c.839G>T (p.Gly280Val)]

NM_000429.3(MAT1A):c.839G>T (p.Gly280Val)

Gene:

MAT1A:methionine adenosyltransferase 1A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q22.3

Genomic location:

Preferred name:

NM_000429.3(MAT1A):c.839G>T (p.Gly280Val)

HGVS:

NC_000010.11:g.80275129C>A
NG_008083.1:g.19550G>T
NM_000429.3:c.839G>TMANE SELECT
NP_000420.1:p.Gly280Val
NC_000010.10:g.82034885C>A

Protein change:

G280V

Molecular consequence:

NM_000429.3:c.839G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hepatic methionine adenosyltransferase deficiency
Synonyms:: MAT I/III DEFICIENCY; Isolated Persistent Hypermethioninemia; Methionine adenosyltransferase deficiency; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009607; MeSH: C564683; MedGen: C0268621; Orphanet: 168598; OMIM: 250850

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004537096	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 16, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31061746, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004537096

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 16, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mild Persistent Isolated Hypermethioninemia Identified through Newborn Screening in Michigan.

Sen K, Felice MD, Bannick A, Colombo R, Conway RL.

J Pediatr Genet. 2019 Jun;8(2):54-57. doi: 10.1055/s-0039-1683900. Epub 2019 Mar 27.

PubMed [citation]

PMID:: 31061746
PMCID:: PMC6499608

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004537096.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MAT1A protein function. This missense change has been observed in individual(s) with MAT1A-related conditions (PMID: 31061746; Invitae). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 280 of the MAT1A protein (p.Gly280Val).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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