NM_001080.3(ALDH5A1):c.79C>T (p.Arg27Cys) AND Succinate-semialdehyde dehydrogenase deficiency

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 17, 2021
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:: RCV001894592.6

Allele description [Variation Report for NM_001080.3(ALDH5A1):c.79C>T (p.Arg27Cys)]

NM_001080.3(ALDH5A1):c.79C>T (p.Arg27Cys)

Genes:

LOC129995978:ATAC-STARR-seq lymphoblastoid silent region 16989 [Gene]
ALDH5A1:aldehyde dehydrogenase 5 family member A1 [Gene - OMIM - HGNC]
GPLD1:glycosylphosphatidylinositol specific phospholipase D1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p22.3

Genomic location:

Preferred name:

NM_001080.3(ALDH5A1):c.79C>T (p.Arg27Cys)

HGVS:

NC_000006.12:g.24495075C>T
NG_008161.1:g.5107C>T
NM_001080.3:c.79C>TMANE SELECT
NM_001368954.1:c.79C>T
NM_170740.1:c.79C>T
NP_001071.1:p.Arg27Cys
NP_001355883.1:p.Arg27Cys
NP_733936.1:p.Arg27Cys
NC_000006.11:g.24495303C>T

Protein change:

R27C

Links:

dbSNP: rs779798309

NCBI 1000 Genomes Browser:

rs779798309

Molecular consequence:

NM_001080.3:c.79C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001368954.1:c.79C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_170740.1:c.79C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Succinate-semialdehyde dehydrogenase deficiency (SSADHD)
Synonyms:: 4-hydroxybutyric aciduria; Gamma-hydroxybutyricaciduria
Identifiers:: MONDO: MONDO:0010083; MedGen: C0268631; Orphanet: 22; OMIM: 271980

Recent activity

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Xenorhabdus nematophila strain YL001 chromosome, complete genome
Xenorhabdus nematophila strain YL001 chromosome, complete genome
gi|1480008974|ref|NZ_CP032329.1|

Nucleotide
stress-70 protein, mitochondrial isoform X1 [Rattus norvegicus]
stress-70 protein, mitochondrial isoform X1 [Rattus norvegicus]
gi|2678910124|ref|XP_063133287.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002127830	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 17, 2021)	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

SCV002127830

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 17, 2021)

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, SCV002127830.3

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

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 not expected to disrupt ALDH5A1 protein function. This variant has not been reported in the literature in individuals affected with ALDH5A1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change replaces arginine with cysteine at codon 27 of the ALDH5A1 protein (p.Arg27Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine.

#	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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