rs727505003
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000195.5(HPS1):c.472C>T(p.Arg158Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000385 in 1,558,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R158H) has been classified as Uncertain significance.
Frequency
Consequence
NM_000195.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HPS1 | NM_000195.5 | c.472C>T | p.Arg158Cys | missense_variant | 6/20 | ENST00000361490.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HPS1 | ENST00000361490.9 | c.472C>T | p.Arg158Cys | missense_variant | 6/20 | 1 | NM_000195.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152206Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000600 AC: 1AN: 166642Hom.: 0 AF XY: 0.0000113 AC XY: 1AN XY: 88396
GnomAD4 exome AF: 0.00000356 AC: 5AN: 1406310Hom.: 0 Cov.: 33 AF XY: 0.00000432 AC XY: 3AN XY: 694380
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74356
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 14, 2014 | The Arg158Cys variant in HPS1 has not been reported in individuals with pulmonar y disease and data from large population studies is insufficient to assess the f requency of this variant. Computational prediction tools and conservation analys es suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, additional info rmation is needed to fully assess the clinical significance of the Arg158Cys var iant. - |
Hermansky-Pudlak syndrome Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | May 10, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at