NM_000531.6(OTC):c.116G>A (p.Gly39Asp) AND OTC-related disorder

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 19, 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:: RCV003892732.1

Allele description [Variation Report for NM_000531.6(OTC):c.116G>A (p.Gly39Asp)]

NM_000531.6(OTC):c.116G>A (p.Gly39Asp)

Gene:

OTC:ornithine transcarbamylase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp11.4

Genomic location:

Preferred name:

NM_000531.6(OTC):c.116G>A (p.Gly39Asp)

HGVS:

NC_000023.11:g.38367329G>A
NG_008471.1:g.19847G>A
NM_000531.6:c.116G>AMANE SELECT
NP_000522.3:p.Gly39Asp
LRG_846t1:c.116G>A
LRG_846:g.19847G>A
LRG_846p1:p.Gly39Asp
NC_000023.10:g.38226582G>A
NM_000531.5:c.116G>A

Protein change:

G39D

Links:

dbSNP: rs1602014500

NCBI 1000 Genomes Browser:

rs1602014500

Molecular consequence:

NM_000531.6:c.116G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: OTC-related disorder
Synonyms:: OTC-related condition
Identifiers:

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004708499	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Oct 19, 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

SCV004708499

PreventionGenetics, part of Exact Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Oct 19, 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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004708499.1

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

Description

The OTC c.116G>A variant is predicted to result in the amino acid substitution p.Gly39Asp. This variant was reported in an individual with suspected ornithine transcarbamylase (OTC) deficiency, although no additional clinical, genetic or functional evidence was provided to help establish pathogenicity (Shchelochkov et al 2009. PubMed ID: 19138872). Other variants impacting the p.Gly39 amino acid (p.Gly39Cys, p.Gly39Ala) have been reported in patients with OTC deficiency (Calvas et al. 1998. PubMed ID: 9452049; Table S2 in Makris et al. 2021. PubMed ID: 33309754), suggesting the p.Gly39 amino acid may be important for OTC function. This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

#	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: May 19, 2024

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