Submissions for variant NM_144687.4(NLRP12):c.236G>A (p.Arg79Gln)

gnomAD frequency: 0.00010  dbSNP: rs144936138

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000695321	SCV000823813	uncertain significance	Familial cold autoinflammatory syndrome 2	2022-10-25	criteria provided, single submitter	clinical testing	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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt NLRP12 protein function. ClinVar contains an entry for this variant (Variation ID: 573609). This variant has not been reported in the literature in individuals affected with NLRP12-related conditions. This variant is present in population databases (rs144936138, gnomAD 0.07%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 79 of the NLRP12 protein (p.Arg79Gln).
CeGaT Center for Human Genetics Tuebingen	RCV001726305	SCV001962219	likely benign	not provided	2021-07-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001726305	SCV002003818	uncertain significance	not provided	2021-04-06	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge