rs6440589
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_032383.5(HPS3):c.1494G>A(p.Gln498=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 1,539,766 control chromosomes in the GnomAD database, including 161,541 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.50 ( 19977 hom., cov: 32)
Exomes 𝑓: 0.45 ( 141564 hom. )
Consequence
HPS3
NM_032383.5 synonymous
NM_032383.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.264
Genes affected
HPS3 (HGNC:15597): (HPS3 biogenesis of lysosomal organelles complex 2 subunit 1) This gene encodes a protein containing a potential clathrin-binding motif, consensus dileucine signals, and tyrosine-based sorting signals for targeting to vesicles of lysosomal lineage. The encoded protein may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. Mutations in this gene are associated with Hermansky-Pudlak syndrome type 3. [provided by RefSeq, Apr 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 3-149155200-G-A is Benign according to our data. Variant chr3-149155200-G-A is described in ClinVar as [Benign]. Clinvar id is 163668.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.264 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HPS3 | NM_032383.5 | c.1494G>A | p.Gln498= | synonymous_variant | 8/17 | ENST00000296051.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HPS3 | ENST00000296051.7 | c.1494G>A | p.Gln498= | synonymous_variant | 8/17 | 1 | NM_032383.5 | P1 | |
HPS3 | ENST00000460120.5 | c.999G>A | p.Gln333= | synonymous_variant | 7/16 | 2 |
Frequencies
GnomAD3 genomes AF: 0.502 AC: 76190AN: 151860Hom.: 19945 Cov.: 32
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GnomAD3 exomes AF: 0.445 AC: 111431AN: 250662Hom.: 25980 AF XY: 0.448 AC XY: 60649AN XY: 135464
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GnomAD4 exome AF: 0.447 AC: 620305AN: 1387788Hom.: 141564 Cov.: 24 AF XY: 0.449 AC XY: 312084AN XY: 694724
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GnomAD4 genome AF: 0.502 AC: 76272AN: 151978Hom.: 19977 Cov.: 32 AF XY: 0.499 AC XY: 37091AN XY: 74302
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 21, 2013 | Gln498Gln in exon 8 of HPS3: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue and is not located withi n the splice consensus sequence. It has been identified in 43.8% (3771/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs6440589). - |
Hermansky-Pudlak syndrome 3 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 10, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 05, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Hermansky-Pudlak syndrome Benign:1
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at