Submissions for variant NM_024747.6(HPS6):c.1A>G (p.Met1Val)

gnomAD frequency: 0.00003  dbSNP: rs763073715

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001860539	SCV002151930	uncertain significance	not provided	2022-03-27	criteria provided, single submitter	clinical testing	This sequence change affects the initiator methionine of the HPS6 mRNA. The next in-frame methionine is located at codon 227. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. Disruption of the initiator codon has been observed in individual(s) with clinical features of Hermansky-Pudlak syndrome (PMID: 32581362). ClinVar contains an entry for this variant (Variation ID: 812730). This variant disrupts a region of the HPS6 protein in which other variant(s) (p.Val128Ala) have been observed in individuals with HPS6-related conditions (PMID: 30369044). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. 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.
Fulgent Genetics, Fulgent Genetics	RCV001003524	SCV002814688	uncertain significance	Hermansky-Pudlak syndrome 6	2022-04-01	criteria provided, single submitter	clinical testing
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001003524	SCV001161834	likely pathogenic	Hermansky-Pudlak syndrome 6		no assertion criteria provided	research