Submissions for variant NM_182476.3(COQ6):c.395A>G (p.Asp132Gly)

gnomAD frequency: 0.00144  dbSNP: rs45496292

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000676228	SCV000251271	uncertain significance	not provided	2018-11-16	criteria provided, single submitter	clinical testing	A variant of unknown significance has been identified in the COQ6 gene. The D132G (c.395 A>G) variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The D132G missense change 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. This substitution occurs at a position that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the D132G variant is damaging to the protein structure/function. Several in silico splice prediction models predict that the c.395 A>G nucleotide substitution, responsible for D132G, creates a cryptic donor site which may supplant the natural donor site and lead to abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. Therefore, based on the currently available information, it is unclear whether the D132G (c.395 A>G) variant is a pathogenic mutation or a rare benign variant.0
Mayo Clinic Laboratories, Mayo Clinic	RCV000676228	SCV000801982	uncertain significance	not provided	2023-06-16	criteria provided, single submitter	clinical testing	BS1, PP3
Invitae	RCV000676228	SCV001023795	likely benign	not provided	2024-01-26	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003937730	SCV004750848	likely benign	COQ6-related condition	2020-09-21	criteria provided, single submitter	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).