11-88335088-GAAAA-GAAAAAAA

Variant names:

• chr11-88335088-G-GAAA
• NM_001814.6:c.173-9_173-7dupTTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001814.6(CTSC):​c.173-9_173-7dupTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000393 in 1,120,236 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.000039 (0 hom.)
• Consequence: CTSC NM_001814.6 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.410

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTSC	NM_001814.6	c.173-9_173-7dupTTT		splice_region_variant, intron_variant	Intron 1 of 6	ENST00000227266.10	NP_001805.4
CTSC	NM_001114173.3	c.173-9_173-7dupTTT		splice_region_variant, intron_variant	Intron 1 of 3		NP_001107645.1
CTSC	NM_148170.5	c.173-9_173-7dupTTT		splice_region_variant, intron_variant	Intron 1 of 3		NP_680475.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTSC	ENST00000227266.10	c.173-9_173-7dupTTT		splice_region_variant, intron_variant	Intron 1 of 6	1	NM_001814.6	ENSP00000227266.4

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.0000393 AC: 44 AN: 1120236 Hom.: 0 Cov.: 16 AF XY: 0.0000195 AC XY: 11 AN XY: 565126

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000277

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000284

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000233

Gnomad4 NFE exome AF: 0.0000480

Gnomad4 OTH exome AF: 0.0000210

GnomAD4 genome Cov.: 29

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-88068256;