ClinVar Miner

Submissions for variant NM_022081.6(HPS4):c.461A>G (p.His154Arg)

dbSNP: rs281865098
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV000020872 SCV003761113 uncertain significance Hermansky-Pudlak syndrome 4 2023-01-24 criteria provided, single submitter curation The p.His154Arg variant in HPS4 has been reported in 3 individuals with Hermansky-Pudlak syndrome 4 (PMID: 12664304, 31898847), segregated with disease in 2 affected relatives from 2 families (PMID: 12664304, 31898847), and has been identified in 0.0009% (1/113688) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs281865098). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported in ClinVar (Variation ID#: 21678) and has been interpreted as pathogenic by OMIM. Of the 3 affected individuals, 1 of those was a homozygote, which increases the likelihood that the p.His154Arg variant is pathogenic (PMID: 31898847). Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM3_supporting, PP1, PP3, PM2_supporting (Richards 2015).
OMIM RCV000020872 SCV000584193 pathogenic Hermansky-Pudlak syndrome 4 2003-07-01 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.