Submissions for variant NM_181882.3(PRX):c.445G>A (p.Ala149Thr)

gnomAD frequency: 0.00193  dbSNP: rs142436391

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000439721	SCV000527792	uncertain significance	not provided	2016-12-19	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the PRX gene. The A149T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The A149T variant is observed in 64/7,182 (0.9%) alleles from individuals of African background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A149T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001079149	SCV000776131	likely benign	Charcot-Marie-Tooth disease type 4	2025-01-20	criteria provided, single submitter	clinical testing
Molecular Genetics Laboratory, London Health Sciences Centre	RCV001173773	SCV001336887	likely benign	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002328964	SCV002638834	likely benign	Inborn genetic diseases	2021-07-20	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
CeGaT Center for Human Genetics Tuebingen	RCV000439721	SCV004143767	likely benign	not provided	2022-09-01	criteria provided, single submitter	clinical testing	PRX: BS2
PreventionGenetics, part of Exact Sciences	RCV003942403	SCV004757520	likely benign	PRX-related disorder	2024-02-09	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).