Submissions for variant NM_006031.6(PCNT):c.9820del (p.Ser3274fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003819016	SCV004613896	pathogenic	not provided	2023-09-19	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ser3274Profs*16) in the PCNT gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PCNT are known to be pathogenic (PMID: 18174396, 22821869). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with PCNT-related conditions. This variant is present in population databases (rs767150246, gnomAD 0.04%).
PreventionGenetics, part of Exact Sciences	RCV004738891	SCV005363478	uncertain significance	PCNT-related disorder	2024-01-12	no assertion criteria provided	clinical testing	The PCNT c.9820delT variant is predicted to result in a frameshift and premature protein termination (p.Ser3274Profs*16). To our knowledge, this variant has not been reported in the literature and no predicted loss-of-function variants have been associated with disease downstream of amino acid 3274. This variant is reported in 0.042% of alleles in individuals of South Asian descent in gnomAD, which is among the most common loss-of-function variants in the database. In addition, it is flagged by gnomAD as having questionable functional consequence. Although we suspect that this variant may be pathogenic, at this time, the clinical significance is uncertain due to the absence of conclusive functional and genetic evidence.