ClinVar

Description

The BBS12 p.Ser328del variant was not identified in the literature nor was it identified in ClinVar or LOVD 3.0. The variant was identified in dbSNP (ID: rs779801356) and in control databases in 50 of 282726 chromosomes at a frequency of 0.0001768 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: Ashkenazi Jewish in 14 of 10368 chromosomes (freq: 0.00135), Other in 2 of 7224 chromosomes (freq: 0.000277), South Asian in 8 of 30600 chromosomes (freq: 0.000261), Latino in 7 of 35426 chromosomes (freq: 0.000198), European (non-Finnish) in 18 of 129084 chromosomes (freq: 0.000139) and European (Finnish) in 1 of 25116 chromosomes (freq: 0.00004), but was not observed in the African or East Asian populations. This variant is an in-frame deletion resulting in the removal of a serine (ser) residue at codon 328; the impact of this alteration on BBS12 protein function is not known. The variant occurs outside of the splicing consensus sequence and three of four in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.