10-102067780-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_024747.6(HPS6):c.2306C>T(p.Pro769Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000167 in 1,612,958 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P769A) has been classified as Uncertain significance.
Frequency
Consequence
NM_024747.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HPS6 | NM_024747.6 | c.2306C>T | p.Pro769Leu | missense_variant | 1/1 | ENST00000299238.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HPS6 | ENST00000299238.7 | c.2306C>T | p.Pro769Leu | missense_variant | 1/1 | NM_024747.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152162Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000813 AC: 2AN: 246144Hom.: 0 AF XY: 0.00000744 AC XY: 1AN XY: 134450
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1460796Hom.: 0 Cov.: 34 AF XY: 0.00000963 AC XY: 7AN XY: 726714
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152162Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74330
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 19, 2015 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 01, 2023 | The c.2306C>T (p.P769L) alteration is located in exon 1 (coding exon 1) of the HPS6 gene. This alteration results from a C to T substitution at nucleotide position 2306, causing the proline (P) at amino acid position 769 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 13, 2022 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 769 of the HPS6 protein (p.Pro769Leu). This variant is present in population databases (rs369970908, gnomAD 0.004%). 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: 435466). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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