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NM_000531.6(OTC):c.722G>A (p.Gly241Asp) AND Ornithine carbamoyltransferase deficiency

Germline classification:
Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:
Jan 22, 2024
Review status:
criteria provided, conflicting classifications
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:
RCV001928943.5

Allele description [Variation Report for NM_000531.6(OTC):c.722G>A (p.Gly241Asp)]

NM_000531.6(OTC):c.722G>A (p.Gly241Asp)

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.722G>A (p.Gly241Asp)
HGVS:
  • NC_000023.11:g.38408880G>A
  • NG_008471.1:g.61398G>A
  • NM_000531.6:c.722G>AMANE SELECT
  • NP_000522.3:p.Gly241Asp
  • LRG_846t1:c.722G>A
  • LRG_846:g.61398G>A
  • LRG_846p1:p.Gly241Asp
  • NC_000023.10:g.38268133G>A
Protein change:
G241D
Links:
dbSNP: rs1461226043
NCBI 1000 Genomes Browser:
rs1461226043
Molecular consequence:
  • NM_000531.6:c.722G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Ornithine carbamoyltransferase deficiency (OTCD)
Synonyms:
ORNITHINE TRANSCARBAMYLASE DEFICIENCY, HYPERAMMONEMIA DUE TO; Ornithine transcarbamylase deficiency; OTC deficiency; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010703; MedGen: C0268542; Orphanet: 664; OMIM: 311250

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV002200269Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Benign
(Jan 22, 2024)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004824440All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain Significance
(Jun 26, 2023)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided108544not providedclinical 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

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 Invitae, SCV002200269.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From All of Us Research Program, National Institutes of Health, SCV004824440.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

This missense variant replaces glycine with aspartic acid at codon 241 of the OTC protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with OTC-related disorders in the literature. This variant has been identified in 1/183224 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown108544not providednot provided1not providednot providednot provided

Last Updated: May 7, 2024