ClinVar Miner

Submissions for variant NM_000195.5(HPS1):c.1406A>G (p.Gln469Arg)

gnomAD frequency: 0.00133  dbSNP: rs148978269
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000888751 SCV001032404 likely benign not provided 2024-01-24 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV001818649 SCV002067228 likely benign not specified 2019-12-02 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002495377 SCV002808044 likely benign Hermansky-Pudlak syndrome 1 2021-11-22 criteria provided, single submitter clinical testing
GeneDx RCV000888751 SCV003803585 uncertain significance not provided 2023-02-09 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published in association with HPS1-related Hermansky-Pudlak syndrome to our knowledge; This variant is associated with the following publications: (PMID: 28719003)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001818649 SCV003845136 likely benign not specified 2023-02-23 criteria provided, single submitter clinical testing Variant summary: HPS1 c.1406A>G (p.Gln469Arg) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00035 in 250958 control chromosomes, predominantly at a frequency of 0.0048 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 5-fold of the estimated maximal expected allele frequency for a pathogenic variant in HPS1 causing Hermansky-Pudlak Syndrome phenotype (0.00096), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.1406A>G in individuals affected with Hermansky-Pudlak Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Five ClinVar submitters (evaluation after 2014) have cited the variant, with four submitters classifying the variant as likely benign and one submitter classifying the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign.
PreventionGenetics, part of Exact Sciences RCV003910533 SCV004726262 likely benign HPS1-related disorder 2021-04-26 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Ambry Genetics RCV004028378 SCV004882584 uncertain significance Inborn genetic diseases 2021-10-27 criteria provided, single submitter clinical testing The c.1406A>G (p.Q469R) alteration is located in exon 15 (coding exon 13) of the HPS1 gene. This alteration results from a A to G substitution at nucleotide position 1406, causing the glutamine (Q) at amino acid position 469 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001273028 SCV001455563 likely benign Hermansky-Pudlak syndrome 2020-09-16 no assertion criteria provided clinical testing

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.