NM_000382.3(ALDH3A2):c.1372C>T (p.Arg458Trp) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 10, 2022
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:: RCV003077685.1

Allele description [Variation Report for NM_000382.3(ALDH3A2):c.1372C>T (p.Arg458Trp)]

NM_000382.3(ALDH3A2):c.1372C>T (p.Arg458Trp)

Gene:

ALDH3A2:aldehyde dehydrogenase 3 family member A2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p11.2

Genomic location:

Preferred name:

NM_000382.3(ALDH3A2):c.1372C>T (p.Arg458Trp)

HGVS:

NC_000017.11:g.19671885C>T
NG_007095.2:g.28135C>T
NM_000382.3:c.1372C>TMANE SELECT
NM_001031806.2:c.1372C>T
NM_001369136.1:c.1372C>T
NM_001369137.2:c.1372C>T
NM_001369138.2:c.1372C>T
NM_001369139.1:c.1372C>T
NM_001369146.2:c.1208-3673C>T
NM_001369148.2:c.793C>T
NP_000373.1:p.Arg458Trp
NP_001026976.1:p.Arg458Trp
NP_001356065.1:p.Arg458Trp
NP_001356066.1:p.Arg458Trp
NP_001356067.1:p.Arg458Trp
NP_001356068.1:p.Arg458Trp
NP_001356077.1:p.Arg265Trp
NC_000017.10:g.19575198C>T

Protein change:

R265W

Molecular consequence:

NM_001369146.2:c.1208-3673C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000382.3:c.1372C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001031806.2:c.1372C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001369136.1:c.1372C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001369137.2:c.1372C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001369138.2:c.1372C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001369139.1:c.1372C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001369148.2:c.793C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: CN517202

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003462294	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 10, 2022)	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

SCV003462294

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 10, 2022)

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 Invitae, SCV003462294.1

#	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 arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 458 of the ALDH3A2 protein (p.Arg458Trp). This variant is present in population databases (rs753900462, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with ALDH3A2-related conditions. 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 ALDH3A2 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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: Feb 13, 2023

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