ClinVar Miner

Submissions for variant NM_198428.3(BBS9):c.767C>T (p.Ser256Leu)

gnomAD frequency: 0.00013  dbSNP: rs149790873
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000803065 SCV000942923 uncertain significance Bardet-Biedl syndrome 2022-08-23 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 256 of the BBS9 protein (p.Ser256Leu). This variant is present in population databases (rs149790873, 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: 648354). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 RCV002534733 SCV003725124 uncertain significance Inborn genetic diseases 2022-11-18 criteria provided, single submitter clinical testing The c.767C>T (p.S256L) alteration is located in exon 8 (coding exon 7) of the BBS9 gene. This alteration results from a C to T substitution at nucleotide position 767, causing the serine (S) at amino acid position 256 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Preventiongenetics, part of Exact Sciences RCV003413609 SCV004109388 uncertain significance BBS9-related condition 2023-02-03 criteria provided, single submitter clinical testing The BBS9 c.767C>T variant is predicted to result in the amino acid substitution p.Ser256Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.064% of alleles in individuals of European (Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/7-33312688-C-T), which may be too common to be an undocumented disease causing variant. 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.

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