Submissions for variant NM_032383.5(HPS3):c.2936A>G (p.Asn979Ser)

gnomAD frequency: 0.00010  dbSNP: rs781373708

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001144199	SCV001304785	uncertain significance	Hermansky-Pudlak syndrome 3	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002557077	SCV003286630	uncertain significance	not provided	2022-11-01	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 979 of the HPS3 protein (p.Asn979Ser). This variant is present in population databases (rs781373708, gnomAD 0.01%). 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: 899562). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt HPS3 protein function. 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.
Ambry Genetics	RCV002559389	SCV003631166	uncertain significance	Inborn genetic diseases	2022-12-19	criteria provided, single submitter	clinical testing	The c.2936A>G (p.N979S) alteration is located in exon 17 (coding exon 17) of the HPS3 gene. This alteration results from a A to G substitution at nucleotide position 2936, causing the asparagine (N) at amino acid position 979 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.