ClinVar Miner

Submissions for variant NM_024747.6(HPS6):c.1819C>T (p.Arg607Ter)

gnomAD frequency: 0.00001  dbSNP: rs377169467
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001942252 SCV002232060 pathogenic not provided 2023-12-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg607*) in the HPS6 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 169 amino acid(s) of the HPS6 protein. This variant is present in population databases (rs377169467, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with Hermansky-Pudlak syndrome (PMID: 29345414, 30387913, 32725903). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1455209). This variant disrupts a region of the HPS6 protein in which other variant(s) (p.Gln680*) have been determined to be pathogenic (PMID: 27225848). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
DASA RCV002221693 SCV002499405 likely pathogenic Hermansky-Pudlak syndrome 6 2022-04-10 criteria provided, single submitter clinical testing The c.1819C>T;p.(Arg607*) variant creates a premature translational stop signal in the HPS6 genewithout sufficient information about prediction of nonsense mediated mRNA decay (NMD) type change; it is present in a relevant exon to the transcript, and disrupts >10% of the protein product. - PVS1_strong. This sequence change has been observed in affected individual(s) (PMID: 30387913) - PS4_supporting. The variant is present at low allele frequencies population databases (rs377169467 – gnomAD 0.0001314%; ABraOM no frequency - https://abraom.ib.usp.br/) - PM2_supporting. The p.(Arg607*) was detected in trans with a pathogenic variant (PMID: 30387913) - PM3. In summary, the currently available evidence indicates that the variant is likely pathogenic.

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