rs753928208
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4_SupportingPP5
The NM_181507.2(HPS5):c.3096_3098del(p.Leu1033del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00000124 in 1,614,040 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. L1032L) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
HPS5
NM_181507.2 inframe_deletion
NM_181507.2 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.79
Genes affected
HPS5 (HGNC:17022): (HPS5 biogenesis of lysosomal organelles complex 2 subunit 2) This gene encodes a protein that may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. This protein interacts with Hermansky-Pudlak syndrome 6 protein and may interact with the cytoplasmic domain of integrin, alpha-3. Mutations in this gene are associated with Hermansky-Pudlak syndrome type 5. Multiple transcript variants encoding two distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_181507.2. Strenght limited to Supporting due to length of the change: 1aa.
PP5
?
Variant 11-18282180-AAGG-A is Pathogenic according to our data. Variant chr11-18282180-AAGG-A is described in ClinVar as [Pathogenic]. Clinvar id is 427877.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-18282180-AAGG-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| HPS5 | NM_181507.2 | c.3096_3098del | p.Leu1033del | inframe_deletion | 22/23 | ENST00000349215.8 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| HPS5 | ENST00000349215.8 | c.3096_3098del | p.Leu1033del | inframe_deletion | 22/23 | 1 | NM_181507.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152158Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461882Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 727244
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152158Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74352
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hermansky-Pudlak syndrome 5 Pathogenic:1
| Pathogenic, no assertion criteria provided | clinical testing | Laboratoire de Génétique Moléculaire, CHU Bordeaux | Mar 14, 2017 | - - |
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at