NM_017570.5(OPLAH):c.3265G>A (p.Val1089Ile) AND 5-Oxoprolinase deficiency

Germline classification:: Benign/Likely benign (4 submissions)
Last evaluated:: Jan 10, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000032836.11

Allele description [Variation Report for NM_017570.5(OPLAH):c.3265G>A (p.Val1089Ile)]

NM_017570.5(OPLAH):c.3265G>A (p.Val1089Ile)

Gene:

OPLAH:5-oxoprolinase, ATP-hydrolysing [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q24.3

Genomic location:

Preferred name:

NM_017570.5(OPLAH):c.3265G>A (p.Val1089Ile)

Other names:

OPLAH, VAL1089ILE (rs185836803)

HGVS:

NC_000008.11:g.144052487C>T
NG_032671.1:g.13195G>A
NM_017570.4:c.3265G>A
NM_017570.5:c.3265G>AMANE SELECT
NP_060040.1:p.Val1089Ile
NC_000008.10:g.145107390C>T
NM_017570.3:c.3265G>A

Protein change:

V1089I; VAL1089ILE

Links:

OMIM: 614243.0003; dbSNP: rs185836803

NCBI 1000 Genomes Browser:

rs185836803

Molecular consequence:

NM_017570.5:c.3265G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: 5-Oxoprolinase deficiency (OPLAHD)
Synonyms:: Oxoprolinuria due to 5-oxoprolinase deficiency; 5-alpha-oxoprolinase deficiency; 5-OXOPROLINURIA DUE TO 5-OXOPROLINASE DEFICIENCY
Identifiers:: MONDO: MONDO:0009825; MedGen: C0268525; Orphanet: 33572; OMIM: 260005; Human Phenotype Ontology: HP:0040142

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000056605	OMIM	no assertion criteria provided	Pathogenic (Jan 1, 2013)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001142394	Reproductive Health Research and Development, BGI Genomics	no assertion criteria provided	Benign (Jan 6, 2020)	germline	curation
SCV001726734	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Jan 10, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002802994	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Aug 16, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

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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, curation
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

5-Oxoprolinuria in Heterozygous Patients for 5-Oxoprolinase (OPLAH) Missense Changes.

Calpena E, Casado M, Martínez-Rubio D, Nascimento A, Colomer J, Gargallo E, García-Cazorla A, Palau F, Artuch R, Espinós C.

JIMD Rep. 2013;7:123-8. doi: 10.1007/8904_2012_166. Epub 2012 Jul 6.

PubMed [citation]

PMID:: 23430506
PMCID:: PMC3575052

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

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000056605.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In an 8-year-old boy with Duchenne muscular dystrophy (310200) due to a deletion in the dystrophin gene (300377), who also had massive excretion of 5-oxoproline in urine but no symptoms related to glutathione cycle defects, Calpena et al. (2013) identified heterozygosity for a 3265G-A transition in the OPLAH gene (SNP rs185836803), resulting in a val1089-to-ile (V1089I) substitution at a relatively conserved residue in the second domain. The presence of a large deletion or duplication was excluded by gel electrophoresis. The mutation was found in heterozygosity in 3 of 154 controls.

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

From Reproductive Health Research and Development, BGI Genomics, SCV001142394.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	not provided

Description

NM_017570.3:c.3265G>A in the OPLAH gene has an allele frequency of 0.024 in Latino subpopulation in the gnomAD database, including 13 homozygous occurrences. It has been detected in heterozygous state in one individual with 5-oxoprolinuria (PMID: 23430506). Taken together, we interprete this variant as Benign/Likely benign variant. ACMG/AMP criteria applied: BS1, BS2, PP4.

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001726734.3

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

#	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

From Fulgent Genetics, Fulgent Genetics, SCV002802994.1

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

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

Last Updated: Nov 3, 2024

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