11-88294073-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001814.6(CTSC):c.1325G>A(p.Arg442His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001814.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152092Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 251004Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135638
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461792Hom.: 0 Cov.: 32 AF XY: 0.0000179 AC XY: 13AN XY: 727188
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152092Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74296
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.1325G>A (p.R442H) alteration is located in exon 7 (coding exon 7) of the CTSC gene. This alteration results from a G to A substitution at nucleotide position 1325, causing the arginine (R) at amino acid position 442 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Papillon-Lefèvre syndrome;C1855627:Haim-Munk syndrome;C4551681:Periodontitis, aggressive 1 Uncertain:1
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 442 of the CTSC protein (p.Arg442His). This variant is present in population databases (rs775201891, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with CTSC-related conditions. ClinVar contains an entry for this variant (Variation ID: 647623). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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