rs104894210
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001814.6(CTSC):c.116G>T(p.Trp39Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000702 in 1,424,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 7.0e-7 ( 0 hom. )
Consequence
CTSC
NM_001814.6 missense
NM_001814.6 missense
Scores
15
3
1
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 6.65
Genes affected
CTSC (HGNC:2528): (cathepsin C) This gene encodes a member of the peptidase C1 family and lysosomal cysteine proteinase that appears to be a central coordinator for activation of many serine proteinases in cells of the immune system. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate heavy and light chains that form a disulfide-linked dimer. A portion of the propeptide acts as an intramolecular chaperone for the folding and stabilization of the mature enzyme. This enzyme requires chloride ions for activity and can degrade glucagon. Defects in the encoded protein have been shown to be a cause of Papillon-Lefevre syndrome, an autosomal recessive disorder characterized by palmoplantar keratosis and periodontitis. [provided by RefSeq, Nov 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.987
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| CTSC | NM_001814.6 | c.116G>T | p.Trp39Leu | missense_variant | Exon 1 of 7 | ENST00000227266.10 | NP_001805.4 | |
| CTSC | NM_001114173.3 | c.116G>T | p.Trp39Leu | missense_variant | Exon 1 of 4 | NP_001107645.1 | ||
| CTSC | NM_148170.5 | c.116G>T | p.Trp39Leu | missense_variant | Exon 1 of 4 | NP_680475.1 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 7.02e-7 AC: 1AN: 1424558Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 705038
GnomAD4 exome
AF:
AC:
1
AN:
1424558
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Cov.:
32
AF XY:
AC XY:
0
AN XY:
705038
Gnomad4 AFR exome
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GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
M;M;M
PrimateAI
Pathogenic
T
PROVEAN
Pathogenic
D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;D;.
Vest4
MutPred
Gain of disorder (P = 0.1157);Gain of disorder (P = 0.1157);Gain of disorder (P = 0.1157);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.