ClinVar Miner

Submissions for variant NM_144687.4(NLRP12):c.104C>T (p.Ala35Val)

gnomAD frequency: 0.00004  dbSNP: rs373357561
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000762037 SCV000892282 uncertain significance not provided 2018-06-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002533892 SCV003444778 uncertain significance Familial cold autoinflammatory syndrome 2 2024-04-05 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 35 of the NLRP12 protein (p.Ala35Val). This variant is present in population databases (rs373357561, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with NLRP12-related conditions. ClinVar contains an entry for this variant (Variation ID: 623965). 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV002533892 SCV003799976 uncertain significance Familial cold autoinflammatory syndrome 2 2022-06-30 criteria provided, single submitter clinical testing The NLRP12 c.104C>T; p.Ala35Val variant (rs373357561), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 623965). This variant is only observed on two alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. The alanine at codon 35 is moderately conserved, but computational analyses predict that this variant is neutral (REVEL: 0.082). Due to limited information, the clinical significance of this variant is uncertain at this time.

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