11-88291569-TGAAAGAAAGAAAGAAAGAAAGAAA-TGAAAGAAAGAAAGAAAGAAAGAAAGAAAGAAAGAAA

Variant names:

• chr11-88291569-T-TGAAAGAAAGAAA
• rs36141641
• ENST00000678554.1:n.890-1063_890-1062insTTTCTTTCTTTC

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The ENST00000678554.1(CTSC):​n.890-1063_890-1062insTTTCTTTCTTTC variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.047 (258 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: CTSC ENST00000678554.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.799

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTSC	ENST00000678554.1	n.890-1063_890-1062insTTTCTTTCTTTC		intron_variant	Intron 6 of 7			ENSP00000504541.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 5990 AN: 126314 Hom.: 258 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0312

Gnomad AMI AF: 0.0686

Gnomad AMR AF: 0.0524

Gnomad ASJ AF: 0.0257

Gnomad EAS AF: 0.0562

Gnomad SAS AF: 0.0227

Gnomad FIN AF: 0.0675

Gnomad MID AF: 0.0286

Gnomad NFE AF: 0.0541

Gnomad OTH AF: 0.0352

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0475 AC: 6000 AN: 126398 Hom.: 258 Cov.: 0 AF XY: 0.0471 AC XY: 2838 AN XY: 60258

Gnomad4 AFR AF: 0.0311

Gnomad4 AMR AF: 0.0525

Gnomad4 ASJ AF: 0.0257

Gnomad4 EAS AF: 0.0561

Gnomad4 SAS AF: 0.0227

Gnomad4 FIN AF: 0.0675

Gnomad4 NFE AF: 0.0542

Gnomad4 OTH AF: 0.0372

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs36141641; hg19: chr11-88024737;