11-88294052-GCA-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_001814.6(CTSC):c.1344_1345delTG(p.Ala449AsnfsTer2) variant causes a frameshift change. The variant allele was found at a frequency of 0.000018 in 1,613,784 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001814.6 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151952Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251052Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135648
GnomAD4 exome AF: 0.0000185 AC: 27AN: 1461832Hom.: 0 AF XY: 0.0000179 AC XY: 13AN XY: 727212
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151952Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74202
ClinVar
Submissions by phenotype
Papillon-Lefèvre syndrome;C1855627:Haim-Munk syndrome;C4551681:Periodontitis, aggressive 1 Uncertain:1
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not provided Uncertain:1
The c.1344_1345delTG variant in the CTSC gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The c.1344_1345delTG variant causes a frameshift starting with codon Alanine 449, changes this amino acid to a Asparagine residue, and creates a premature Stop codon at position 2 of the new reading frame, denoted p.Ala449AsnfsX2. This variant is predicted to cause loss of normal protein function through protein truncation. The c.1344_1345delTG variant was not observed at any significant frequency in approximately 6,500 individuals of European and African American ancestry by the NHLBI Exome Sequencing Project. We interpret c.1344_1345delTG as a variant of uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at