Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001924191 | SCV002207433 | pathogenic | not provided | 2021-02-20 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with HPS3-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ser12*) in the HPS3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HPS3 are known to be pathogenic (PMID: 11590544). |
| Neuberg Centre For Genomic Medicine, |
RCV003448433 | SCV004176601 | likely pathogenic | Hermansky-Pudlak syndrome 3 | 2023-02-14 | criteria provided, single submitter | clinical testing | The stop gain c.35C>A (p.Ser12Ter) variant in HPS3 gene has been reported to ClinVar as a Pathogenic, but no details are available for independent assessment. The p.Ser12Ter variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. The nucleotide change c.35C>A in HPS3 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Likely Pathogenic. |