ClinVar Miner

Submissions for variant NM_001199138.2(NLRC4):c.1550G>C (p.Cys517Ser)

gnomAD frequency: 0.00003  dbSNP: rs779390608
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002262085 SCV002542374 uncertain significance Autoinflammatory syndrome 2021-06-24 criteria provided, single submitter clinical testing
Ambry Genetics RCV003095941 SCV003610121 likely benign Inborn genetic diseases 2022-03-29 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CeGaT Center for Human Genetics Tuebingen RCV003222408 SCV003916085 likely benign not provided 2023-02-01 criteria provided, single submitter clinical testing NLRC4: BP4
Invitae RCV003774822 SCV004571336 uncertain significance Periodic fever-infantile enterocolitis-autoinflammatory syndrome; Familial cold autoinflammatory syndrome 4 2024-01-25 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 517 of the NLRC4 protein (p.Cys517Ser). This variant is present in population databases (rs779390608, gnomAD 0.007%). 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: 1694363). 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.

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