ClinVar Miner

Submissions for variant NM_001166114.2(PNPLA6):c.3997G>A (p.Ala1333Thr)

gnomAD frequency: 0.00014  dbSNP: rs143280550
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001848584 SCV002105527 uncertain significance Hereditary spastic paraplegia 2021-10-21 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002543422 SCV003245451 uncertain significance Hereditary spastic paraplegia 39 2022-08-16 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1295 of the PNPLA6 protein (p.Ala1295Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 1344481). 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. 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 RCV002543421 SCV003622142 uncertain significance Inborn genetic diseases 2022-05-09 criteria provided, single submitter clinical testing The c.3883G>A (p.A1295T) alteration is located in exon 34 (coding exon 32) of the PNPLA6 gene. This alteration results from a G to A substitution at nucleotide position 3883, causing the alanine (A) at amino acid position 1295 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.