ClinVar Miner

Submissions for variant NM_032383.5(HPS3):c.728_729insA (p.Ser244fs)

gnomAD frequency: 0.00001  dbSNP: rs760577035
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001939475 SCV002234777 pathogenic not provided 2024-05-06 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser244Phefs*4) 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). This variant is present in population databases (rs760577035, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with HPS3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1454368). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV003475220 SCV004200013 pathogenic Hermansky-Pudlak syndrome 3 2024-02-04 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV003475220 SCV005662856 pathogenic Hermansky-Pudlak syndrome 3 2024-03-29 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV005057830 SCV005727170 pathogenic Hermansky-Pudlak syndrome 2024-11-04 criteria provided, single submitter clinical testing Variant summary: HPS3 c.728_729insA (p.Ser244PhefsX4) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 8e-06 in 251068 control chromosomes. c.728_729insA has been reported in the literature in a homozygous individual affected with Hermansky-Pudlak Syndrome (Huizing_2020). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 31898847). ClinVar contains an entry for this variant (Variation ID: 1454368). Based on the evidence outlined above, the variant was classified as pathogenic.

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