chr11-88294350-CT-C
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_001814.6(CTSC):c.1047delA(p.Gly350ValfsTer10) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_001814.6 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251074Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135670
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Papillon-Lefèvre syndrome Pathogenic:1
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Papillon-Lefèvre syndrome;C1855627:Haim-Munk syndrome;C4551681:Periodontitis, aggressive 1 Pathogenic:1
This variant is present in population databases (rs587776655, gnomAD 0.0009%). For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the CTSC protein in which other variant(s) (p.Trp429*) have been determined to be pathogenic (PMID: 10593994, 28242153, 29410039). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 7293). This variant is also known as 2692delA. This premature translational stop signal has been observed in individual(s) with Papillon-Lefèvre syndrome (PMID: 10593994). This sequence change creates a premature translational stop signal (p.Gly350Valfs*10) in the CTSC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 114 amino acid(s) of the CTSC protein. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at