rs281865078
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Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_000195.5(HPS1):c.418delG(p.Ala140fs) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000715 in 1,398,318 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 7.2e-7 ( 0 hom. )
Consequence
HPS1
NM_000195.5 frameshift
NM_000195.5 frameshift
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 4.47
Genes affected
HPS1 (HGNC:5163): (HPS1 biogenesis of lysosomal organelles complex 3 subunit 1) This gene encodes a protein that may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. The encoded protein is a component of three different protein complexes termed biogenesis of lysosome-related organelles complex (BLOC)-3, BLOC4, and BLOC5. Mutations in this gene are associated with Hermansky-Pudlak syndrome type 1. Alternative splicing results in multiple transcript variants. A pseudogene related to this gene is located on chromosome 22. [provided by RefSeq, Aug 2015]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HPS1 | NM_000195.5 | c.418delG | p.Ala140fs | frameshift_variant | 6/20 | ENST00000361490.9 | NP_000186.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HPS1 | ENST00000361490.9 | c.418delG | p.Ala140fs | frameshift_variant | 6/20 | 1 | NM_000195.5 | ENSP00000355310.4 | ||
ENSG00000289758 | ENST00000699159.1 | n.418delG | non_coding_transcript_exon_variant | 6/24 | ENSP00000514167.1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD4 exome AF: 7.15e-7 AC: 1AN: 1398318Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 689796
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33
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689796
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GnomAD4 genome Cov.: 31
GnomAD4 genome
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31
ClinVar
Not reported inComputational scores
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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