Submissions for variant NM_000531.6(OTC):c.140A>C (p.Asn47Thr)

gnomAD frequency: 0.00011  dbSNP: rs67939655

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000454814	SCV000539982	likely benign	not specified	2020-06-11	criteria provided, single submitter	clinical testing	The p.Asn47Thr variant in OTC is classified as likely benign because although it has been reported in 1 female with ornithine transcarbamylase (OTC) deficiency (PMID 16786505), it has also been identified in 14/75447 hemizygous males in gnomAD (http://gnomad.broadinstitute.org), which is an allele frequency too high to cause OTC deficiency. ACMG/AMP criteria applied:BS1, BS4.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000148720	SCV001419035	benign	Ornithine carbamoyltransferase deficiency	2025-01-30	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000148720	SCV002033205	uncertain significance	Ornithine carbamoyltransferase deficiency	2021-11-07	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004955272	SCV005460653	benign	Inborn genetic diseases	2024-10-21	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GenMed Metabolism Lab	RCV000083340	SCV000115426	pathogenic	not provided		no assertion criteria provided	not provided	Converted during submission to Pathogenic.
CSER _CC_NCGL, University of Washington	RCV000148720	SCV000190452	uncertain significance	Ornithine carbamoyltransferase deficiency	2014-06-01	no assertion criteria provided	research
Natera, Inc.	RCV000148720	SCV002087162	uncertain significance	Ornithine carbamoyltransferase deficiency	2020-02-25	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003945033	SCV004762875	likely benign	OTC-related disorder	2022-08-10	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).