chr10-102065728-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_024747.6(HPS6):c.254C>T(p.Pro85Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000139 in 1,502,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_024747.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HPS6 | NM_024747.6 | c.254C>T | p.Pro85Leu | missense_variant | 1/1 | ENST00000299238.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HPS6 | ENST00000299238.7 | c.254C>T | p.Pro85Leu | missense_variant | 1/1 | NM_024747.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000138 AC: 21AN: 151980Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000340 AC: 34AN: 100116Hom.: 0 AF XY: 0.000303 AC XY: 17AN XY: 56016
GnomAD4 exome AF: 0.000139 AC: 188AN: 1350870Hom.: 0 Cov.: 31 AF XY: 0.000138 AC XY: 92AN XY: 666376
GnomAD4 genome ? AF: 0.000138 AC: 21AN: 151980Hom.: 0 Cov.: 33 AF XY: 0.000202 AC XY: 15AN XY: 74246
ClinVar
Submissions by phenotype
Hermansky-Pudlak syndrome 6 Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Zotz-Klimas Genetics Lab, MVZ Zotz Klimas | Nov 24, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Feb 28, 2022 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 31, 2017 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 27, 2022 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 85 of the HPS6 protein (p.Pro85Leu). This variant is present in population databases (rs544314793, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with HPS6-related conditions. ClinVar contains an entry for this variant (Variation ID: 435463). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt HPS6 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at