ClinVar Miner

Submissions for variant NM_001199138.2(NLRC4):c.952G>C (p.Ala318Pro)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV003262484 SCV003985091 uncertain significance Inborn genetic diseases 2023-05-09 criteria provided, single submitter clinical testing The c.952G>C (p.A318P) alteration is located in exon 4 (coding exon 3) of the NLRC4 gene. This alteration results from a G to C substitution at nucleotide position 952, causing the alanine (A) at amino acid position 318 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003779989 SCV004591658 uncertain significance Periodic fever-infantile enterocolitis-autoinflammatory syndrome; Familial cold autoinflammatory syndrome 4 2023-10-25 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 318 of the NLRC4 protein (p.Ala318Pro). This variant is present in population databases (rs779778729, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with NLRC4-related conditions. ClinVar contains an entry for this variant (Variation ID: 2545626). 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 expected to disrupt NLRC4 protein function with a positive 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.

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