Submissions for variant NM_001166114.2(PNPLA6):c.29C>G (p.Thr10Arg)

gnomAD frequency: 0.00004  dbSNP: rs777466386

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
New York Genome Center	RCV002227741	SCV002506843	uncertain significance	Ataxia-hypogonadism-choroidal dystrophy syndrome; Laurence-Moon syndrome; Hereditary spastic paraplegia 39; Trichomegaly-retina pigmentary degeneration-dwarfism syndrome	2021-07-16	criteria provided, single submitter	clinical testing	The inherited c.29C>G (p.Thr10Arg) variant identified in the PNPLA6 gene substitutes a moderately conserved Threonine for Arginine at amino acid 10/1366 (exon 1/32). This variant is found with low frequency in gnomAD(v3.1.1) (5 heterozygotes, 0 homozygotes; allele frequency: 3.29e-5) suggesting it is not a common benign variant in the populations represented in that database. In silico algorithms predict this variant to be Damaging (SIFT; score: 0.007) andBenign (REVEL; score: 0.1609) to the function of the canonical transcript. It is absent from ClinVar and to our current knowledge has not been reported in affectedindividuals in the literature. The p.Thr10 residue is not within a mapped domain of PNPLA6 (UniProtKB:Q8IY17). Given the lack of compelling evidence for itspathogenicity, the inherited c.29C>G (p.Thr10Arg) variant identified in the PNPLA6 gene is reported as a Variant of Uncertain Significance.