ClinVar Miner

Submissions for variant NM_000064.4(C3):c.4667A>G (p.Asn1556Ser)

gnomAD frequency: 0.00014  dbSNP: rs139381845
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001312779 SCV001503247 uncertain significance not provided 2023-12-11 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1556 of the C3 protein (p.Asn1556Ser). This variant is present in population databases (rs139381845, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with C3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1014094). 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 C3 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.
Fulgent Genetics, Fulgent Genetics RCV002476444 SCV002775934 uncertain significance Age related macular degeneration 9; Atypical hemolytic-uremic syndrome with C3 anomaly; Complement component 3 deficiency 2021-07-23 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003945990 SCV004760135 uncertain significance C3-related disorder 2024-01-24 no assertion criteria provided clinical testing The C3 c.4667A>G variant is predicted to result in the amino acid substitution p.Asn1556Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.013% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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