Submissions for variant NM_033109.5(PNPT1):c.516C>T (p.Gly172=)

gnomAD frequency: 0.00009  dbSNP: rs372627112

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000609864	SCV000732620	likely benign	not specified	2017-06-23	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001860354	SCV002155094	uncertain significance	not provided	2022-05-29	criteria provided, single submitter	clinical testing	This sequence change affects codon 172 of the PNPT1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the PNPT1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs372627112, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with PNPT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 518028). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
PreventionGenetics, part of Exact Sciences	RCV004544803	SCV004777981	likely benign	PNPT1-related disorder	2019-08-20	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).