11-88291569-T-TGAAAGAAAGAAAGAAAGAAA

Variant summary

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

The ENST00000678554.1(CTSC):c.890-1063_890-1062insTTTCTTTCTTTCTTTCTTTC variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.14 (1825 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: CTSC ENST00000678554.1 intron, NMD_transcript
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• 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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTSC	ENST00000678554.1	c.890-1063_890-1062insTTTCTTTCTTTCTTTCTTTC		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00 AC: 17572 AN: 126108 Hom.: 1823 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0785

Gnomad AMI AF: 0.0748

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.0236

Gnomad SAS AF: 0.0999

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.155

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: 0.139 AC: 17574 AN: 126192 Hom.: 1825 Cov.: 0 AF XY: 0.133 AC XY: 7988 AN XY: 60168

Gnomad4 AFR AF: 0.0784

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.0236

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.154

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Department of Pathology and Laboratory Medicine, Sinai Health System

-

- -

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;