ClinVar Miner

Submissions for variant NM_144687.4(NLRP12):c.154G>A (p.Gly52Ser)

gnomAD frequency: 0.00011  dbSNP: rs369053968
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000541640 SCV000646326 uncertain significance Familial cold autoinflammatory syndrome 2 2024-01-25 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 52 of the NLRP12 protein (p.Gly52Ser). This variant is present in population databases (rs369053968, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with clinical features of familial cold autoinflammatory syndrome (FCAS) (PMID: 29500522). ClinVar contains an entry for this variant (Variation ID: 469089). 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 with a negative predictive value of 80%. 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.
GeneDx RCV001755852 SCV001994935 uncertain significance not provided 2020-01-31 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29500522, 30783801)
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002263784 SCV002542455 uncertain significance Autoinflammatory syndrome 2018-05-01 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV001755852 SCV004225439 uncertain significance not provided 2022-02-17 criteria provided, single submitter clinical testing BP4

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