Submissions for variant NM_198428.3(BBS9):c.1559C>T (p.Pro520Leu)

gnomAD frequency: 0.00021  dbSNP: rs769669385

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000791063	SCV000930332	uncertain significance	not specified	2019-04-27	criteria provided, single submitter	clinical testing
Invitae	RCV001201677	SCV001372760	uncertain significance	Bardet-Biedl syndrome	2023-11-27	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 520 of the BBS9 protein (p.Pro520Leu). This variant is present in population databases (rs769669385, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with BBS9-related conditions. ClinVar contains an entry for this variant (Variation ID: 638414). 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 BBS9 protein function with a negative predictive value of 80%. 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.
PreventionGenetics, part of Exact Sciences	RCV003396374	SCV004110080	uncertain significance	BBS9-related condition	2023-10-11	criteria provided, single submitter	clinical testing	The BBS9 c.1559C>T variant is predicted to result in the amino acid substitution p.Pro520Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.051% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/7-33397473-C-T). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Clinical Genetics, Academic Medical Center	RCV001701442	SCV001920758	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001701442	SCV001951029	uncertain significance	not provided		no assertion criteria provided	clinical testing