NM_000687.4(AHCY):c.1190C>T (p.Ala397Val) AND Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 10, 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:: RCV002036111.4

Allele description [Variation Report for NM_000687.4(AHCY):c.1190C>T (p.Ala397Val)]

NM_000687.4(AHCY):c.1190C>T (p.Ala397Val)

Gene:

AHCY:adenosylhomocysteinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

20q11.22

Genomic location:

Preferred name:

NM_000687.4(AHCY):c.1190C>T (p.Ala397Val)

HGVS:

NC_000020.11:g.34281143G>A
NG_012630.2:g.35660C>T
NM_000687.2:c.1190C>T
NM_000687.4:c.1190C>TMANE SELECT
NM_001161766.2:c.1106C>T
NM_001322084.2:c.1106C>T
NM_001322085.2:c.1106C>T
NM_001322086.2:c.1196C>T
NM_001362750.2:c.1190C>T
NP_000678.1:p.Ala397Val
NP_001155238.1:p.Ala369Val
NP_001309013.1:p.Ala369Val
NP_001309014.1:p.Ala369Val
NP_001309015.1:p.Ala399Val
NP_001349679.1:p.Ala397Val
NC_000020.10:g.32868949G>A

Protein change:

A369V

Links:

dbSNP: rs202122223

NCBI 1000 Genomes Browser:

rs202122223

Molecular consequence:

NM_000687.4:c.1190C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001161766.2:c.1106C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001322084.2:c.1106C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001322085.2:c.1106C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001322086.2:c.1196C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001362750.2:c.1190C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase
Synonyms:: Hypermethioninemia with s-adenosylhomocysteine hydrolase deficiency
Identifiers:: MONDO: MONDO:0013404; MedGen: C3151058; Orphanet: 88618; OMIM: 613752

Recent activity

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Mus musculus mitogen-activated protein kinase kinase kinase 2 (Map3k2), mRNA
Mus musculus mitogen-activated protein kinase kinase kinase 2 (Map3k2), mRNA
gi|169234761|ref|NM_011946.3|

Nucleotide
Mus musculus BAC clone RP23-302E1 from chromosome 12, complete sequence
Mus musculus BAC clone RP23-302E1 from chromosome 12, complete sequence
gi|63004101|gb|AC154636.2||gnl|wugs 3-302E1

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002310926	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 10, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002310926

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 10, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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, SCV002310926.3

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

Description

This sequence change replaces alanine with valine at codon 397 of the AHCY protein (p.Ala397Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs202122223, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with AHCY-related conditions. ClinVar contains an entry for this variant (Variation ID: 1522574). 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 not expected to disrupt AHCY protein function with a negative predictive value of 80%. 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.

#	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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