ClinVar Miner

Submissions for variant NM_001166114.2(PNPLA6):c.881C>T (p.Ala294Val)

gnomAD frequency: 0.00002  dbSNP: rs756180538
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001063537 SCV001228386 uncertain significance Hereditary spastic paraplegia 39 2022-10-05 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 857794). This variant has not been reported in the literature in individuals affected with PNPLA6-related conditions. This variant is present in population databases (rs756180538, gnomAD 0.009%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 255 of the PNPLA6 protein (p.Ala255Val).
Illumina Laboratory Services, Illumina RCV001063537 SCV001295600 uncertain significance Hereditary spastic paraplegia 39 2018-03-02 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001847144 SCV002105538 uncertain significance Hereditary spastic paraplegia 2017-07-11 criteria provided, single submitter clinical testing
Ambry Genetics RCV002555823 SCV003655505 uncertain significance Inborn genetic diseases 2022-10-26 criteria provided, single submitter clinical testing The c.764C>T (p.A255V) alteration is located in exon 10 (coding exon 8) of the PNPLA6 gene. This alteration results from a C to T substitution at nucleotide position 764, causing the alanine (A) at amino acid position 255 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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