ClinVar Miner

Submissions for variant NM_001166114.2(PNPLA6):c.3104C>T (p.Ser1035Leu)

gnomAD frequency: 0.00001  dbSNP: rs541098659
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001859389 SCV002283674 pathogenic Hereditary spastic paraplegia 39 2022-11-01 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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 PNPLA6 protein function. ClinVar contains an entry for this variant (Variation ID: 1195875). This variant is also known as c.3134C>T (p.Ser1045Leu). This missense change has been observed in individual(s) with Boucher-Neuhäuser syndrome and/or Oliver-McFarlane syndrome (PMID: 24355708, 25267340, 33141049). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs541098659, gnomAD 0.003%). This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 997 of the PNPLA6 protein (p.Ser997Leu).
GeneReviews RCV001559127 SCV001781212 not provided Ataxia-hypogonadism-choroidal dystrophy syndrome no assertion provided literature only To date reported only in compound heterozygotes with Boucher-Neuhauser syndrome

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