ClinVar Miner

Submissions for variant NM_000744.7(CHRNA4):c.985A>G (p.Asn329Asp)

gnomAD frequency: 0.00001  dbSNP: rs767865433
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489588 SCV000576590 uncertain significance not provided 2017-04-26 criteria provided, single submitter clinical testing The N329D variant in the CHRNA4 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The N329D variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The N329D variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret N329D as a variant of uncertain significance.
Invitae RCV003746528 SCV004464534 uncertain significance Autosomal dominant nocturnal frontal lobe epilepsy 2023-06-23 criteria provided, single submitter clinical testing 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. 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 CHRNA4 protein function. ClinVar contains an entry for this variant (Variation ID: 426205). This variant has not been reported in the literature in individuals affected with CHRNA4-related conditions. This variant is present in population databases (rs767865433, gnomAD 0.1%). This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 329 of the CHRNA4 protein (p.Asn329Asp).

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