rs2689232
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Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1
The NM_032383.5(HPS3):c.1164-25C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,606,278 control chromosomes in the GnomAD database, including 41,521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..
Frequency
Genomes: 𝑓 0.18 ( 3072 hom., cov: 31)
Exomes 𝑓: 0.22 ( 38449 hom. )
Consequence
HPS3
NM_032383.5 intron
NM_032383.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.541
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 -18 ACMG points.
BP4
This place is a probable branch point but likely benign (scored 3 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.28).
BP6
Variant 3-149150574-C-T is Benign according to our data. Variant chr3-149150574-C-T is described in ClinVar as [Benign]. Clinvar id is 262023.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HPS3 | NM_032383.5 | c.1164-25C>T | intron_variant | ENST00000296051.7 | NP_115759.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HPS3 | ENST00000296051.7 | c.1164-25C>T | intron_variant | 1 | NM_032383.5 | ENSP00000296051.2 | ||||
HPS3 | ENST00000460120.5 | c.669-25C>T | intron_variant | 2 | ENSP00000418230.1 | |||||
HPS3 | ENST00000462030.5 | n.1763-25C>T | intron_variant | 2 | ||||||
HPS3 | ENST00000486530.1 | n.1197-25C>T | intron_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.181 AC: 27466AN: 152034Hom.: 3075 Cov.: 31
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GnomAD3 exomes AF: 0.212 AC: 53155AN: 250742Hom.: 6242 AF XY: 0.220 AC XY: 29854AN XY: 135508
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GnomAD4 exome AF: 0.224 AC: 326012AN: 1454126Hom.: 38449 Cov.: 30 AF XY: 0.227 AC XY: 164363AN XY: 723866
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GnomAD4 genome AF: 0.181 AC: 27468AN: 152152Hom.: 3072 Cov.: 31 AF XY: 0.185 AC XY: 13720AN XY: 74362
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 09, 2018 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Hermansky-Pudlak syndrome 3 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 10, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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BranchPoint Hunter
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at