ClinVar Miner

Submissions for variant NM_001199138.2(NLRC4):c.2647G>A (p.Ala883Thr)

gnomAD frequency: 0.00007  dbSNP: rs780229500
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000796870 SCV000936402 uncertain significance Periodic fever-infantile enterocolitis-autoinflammatory syndrome; Familial cold autoinflammatory syndrome 4 2024-01-26 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 883 of the NLRC4 protein (p.Ala883Thr). This variant is present in population databases (rs780229500, gnomAD 0.009%). 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: 643212). 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 NLRC4 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.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002263988 SCV002542396 likely benign Autoinflammatory syndrome 2016-12-12 criteria provided, single submitter clinical testing
Ambry Genetics RCV002534612 SCV003740643 uncertain significance Inborn genetic diseases 2021-12-17 criteria provided, single submitter clinical testing The c.2647G>A (p.A883T) alteration is located in exon 8 (coding exon 7) of the NLRC4 gene. This alteration results from a G to A substitution at nucleotide position 2647, causing the alanine (A) at amino acid position 883 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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