rs11326739

Variant names:

• chr11-88335088-GAAAA-G
• NM_001814.6:c.173-10_173-7delTTTT

Your query was ambiguous. Multiple possible variants found:

• chr11-88335088-GAAAA-G
• chr11-88335088-GAAAA-GA
• chr11-88335088-GAAAA-GAA
• chr11-88335088-GAAAA-GAAA
• chr11-88335088-GAAAA-GAAAAA
• chr11-88335088-GAAAA-GAAAAAA
• chr11-88335088-GAAAA-GAAAAAAA
• chr11-88335088-GAAAA-GAAAAAAAA

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001814.6(CTSC):​c.173-10_173-7delTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000357 in 1,120,460 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: CTSC NM_001814.6 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.82

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.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 11-88335088-GAAAA-G is Benign according to our data. Variant chr11-88335088-GAAAA-G is described in ClinVar as [Likely_benign]. Clinvar id is 2951257.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTSC	NM_001814.6	c.173-10_173-7delTTTT		splice_region_variant, intron_variant	Intron 1 of 6	ENST00000227266.10	NP_001805.4
CTSC	NM_001114173.3	c.173-10_173-7delTTTT		splice_region_variant, intron_variant	Intron 1 of 3		NP_001107645.1
CTSC	NM_148170.5	c.173-10_173-7delTTTT		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.173-10_173-7delTTTT		splice_region_variant, intron_variant	Intron 1 of 6	1	NM_001814.6	ENSP00000227266.4

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000357 AC: 4 AN: 1120460 Hom.: 0 AF XY: 0.00000354 AC XY: 2 AN XY: 565232

Gnomad4 AFR exome AF: 0.0000386

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000138

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000240

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Papillon-Lefèvre syndrome;C1855627:Haim-Munk syndrome;C4551681:Periodontitis, aggressive 1 Benign:1

Jul 22, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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;