rs104894214
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM1PM2PM5PP3_StrongPP5_Moderate
The NM_001814.6(CTSC):c.901G>A(p.Gly301Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 1,613,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (â ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G301V) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001814.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CTSC | NM_001814.6 | c.901G>A | p.Gly301Ser | missense_variant | 7/7 | ENST00000227266.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTSC | ENST00000227266.10 | c.901G>A | p.Gly301Ser | missense_variant | 7/7 | 1 | NM_001814.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152150Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000359 AC: 9AN: 251042Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135696
GnomAD4 exome AF: 0.0000233 AC: 34AN: 1461808Hom.: 0 Cov.: 31 AF XY: 0.0000275 AC XY: 20AN XY: 727200
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152150Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74322
ClinVar
Submissions by phenotype
Papillon-Lefèvre syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 01, 2001 | - - |
Papillon-Lefèvre syndrome;C1855627:Haim-Munk syndrome;C4551681:Periodontitis, aggressive 1 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 22, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 301 of the CTSC protein (p.Gly301Ser). This variant is present in population databases (rs104894214, gnomAD 0.01%). This missense change has been observed in individuals with Papillon-LefâÂŽvre syndrome (PMID: 10581027, 11180012). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 7297). 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 expected to disrupt CTSC protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at