rs281865101
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_181507.2(HPS5):c.879dupC(p.Lys294GlnfsTer6) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,455,752 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_181507.2 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HPS5 | ENST00000349215.8 | c.879dupC | p.Lys294GlnfsTer6 | frameshift_variant | Exon 8 of 23 | 1 | NM_181507.2 | ENSP00000265967.5 | ||
HPS5 | ENST00000396253.7 | c.537dupC | p.Lys180GlnfsTer6 | frameshift_variant | Exon 7 of 22 | 1 | ENSP00000379552.3 | |||
HPS5 | ENST00000438420.6 | c.537dupC | p.Lys180GlnfsTer6 | frameshift_variant | Exon 7 of 22 | 1 | ENSP00000399590.2 | |||
HPS5 | ENST00000531848.1 | c.537dupC | p.Lys180GlnfsTer6 | frameshift_variant | Exon 7 of 11 | 5 | ENSP00000431758.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1455752Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1AN XY: 724652
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Hermansky-Pudlak syndrome 5 Pathogenic:1
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not provided Pathogenic:1
This sequence change creates a premature translational stop signal (p.Lys294Glnfs*6) in the HPS5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HPS5 are known to be pathogenic (PMID: 12548288, 15296495, 21833017, 26785811). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Hermansky–Pudlak syndrome (PMID: 15296495). This variant is also known as P293insC. ClinVar contains an entry for this variant (Variation ID: 21822). For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at