NM_003748.4(ALDH4A1):c.1504G>A (p.Gly502Ser) AND Hyperprolinemia type 2

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 7, 2020
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:: RCV001301545.6

Allele description

NM_003748.4(ALDH4A1):c.1504G>A (p.Gly502Ser)

Gene:

ALDH4A1:aldehyde dehydrogenase 4 family member A1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.13

Genomic location:

Preferred name:

NM_003748.4(ALDH4A1):c.1504G>A (p.Gly502Ser)

HGVS:

NC_000001.11:g.18874538C>T
NG_012283.1:g.33262G>A
NM_001161504.2:c.1324G>A
NM_001319218.2:c.1351G>A
NM_003748.4:c.1504G>AMANE SELECT
NM_170726.3:c.1504G>A
NP_001154976.1:p.Gly442Ser
NP_001306147.1:p.Gly451Ser
NP_003739.2:p.Gly502Ser
NP_733844.1:p.Gly502Ser
NC_000001.10:g.19201032C>T

Protein change:

G442S

Links:

dbSNP: rs766982473

NCBI 1000 Genomes Browser:

rs766982473

Molecular consequence:

NM_001161504.2:c.1324G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001319218.2:c.1351G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003748.4:c.1504G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_170726.3:c.1504G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hyperprolinemia type 2 (HYRPRO2)
Synonyms:: 1-PYRROLINE-5-CARBOXYLATE DEHYDROGENASE DEFICIENCY; Delta-1-pyrroline-5-carboxylate dehydrogenase deficiency; Deficiency of pyrroline-5-carboxylate reductase
Identifiers:: MONDO: MONDO:0009401; MedGen: C2931835; Orphanet: 79101; OMIM: 239510

Recent activity

Clear Turn Off Turn On

probable 2-oxoglutarate-dependent dioxygenase SLC1 [Oryza sativa Japonica Group]
probable 2-oxoglutarate-dependent dioxygenase SLC1 [Oryza sativa Japonica Group]
gi|1002288325|ref|XP_015648463.1|

Protein
MULTISPECIES: DUF192 domain-containing protein [Pseudomonadota]
MULTISPECIES: DUF192 domain-containing protein [Pseudomonadota]
gi|505085295|ref|WP_015272397.1|

Protein
GM12878_SA1_1.2
GM12878_SA1_1.2

biosample
PREDICTED: Pan paniscus syndecan 3 (SDC3), transcript variant X2, mRNA
PREDICTED: Pan paniscus syndecan 3 (SDC3), transcript variant X2, mRNA
gi|2694380349|ref|XM_034959753.3|

Nucleotide
PREDICTED: Mus musculus transmembrane protein 63c (Tmem63c), transcript variant ...
PREDICTED: Mus musculus transmembrane protein 63c (Tmem63c), transcript variant X4, mRNA
gi|1907086957|ref|XM_011244085.4|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001490717	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 7, 2020)	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

SCV001490717

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 7, 2020)

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, SCV001490717.4

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

Description

Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with ALDH4A1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with serine at codon 502 of the ALDH4A1 protein (p.Gly502Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. 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: Jun 17, 2024

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