ClinVar Miner

Submissions for variant NM_001166114.2(PNPLA6):c.1096G>C (p.Ala366Pro)

gnomAD frequency: 0.00013  dbSNP: rs533164657
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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 RCV001227145 SCV001399487 uncertain significance Hereditary spastic paraplegia 39 2024-01-03 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 327 of the PNPLA6 protein (p.Ala327Pro). This variant is present in population databases (rs533164657, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with PNPLA6-related conditions. ClinVar contains an entry for this variant (Variation ID: 954647). 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 PNPLA6 protein function with a negative predictive value of 95%. 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.
Ambry Genetics RCV004659417 SCV005148369 uncertain significance Inborn genetic diseases 2024-04-17 criteria provided, single submitter clinical testing The c.979G>C (p.A327P) alteration is located in exon 12 (coding exon 10) of the PNPLA6 gene. This alteration results from a G to C substitution at nucleotide position 979, causing the alanine (A) at amino acid position 327 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
CeGaT Center for Human Genetics Tuebingen RCV004809538 SCV005433470 uncertain significance not provided 2024-11-01 criteria provided, single submitter clinical testing PNPLA6: PM2

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