Variant chr11-88335088-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_001814.6(CTSC):c.173-6C>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000883 in 1,120,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in Lovd as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000028 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000088 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CTSC
NM_001814.6 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00006288

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.26

Variant links:

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]

CTSC links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 11-88335088-G-T is Benign according to our data. Variant chr11-88335088-G-T is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
CTSC	NM_001814.6 linkuse as main transcript	c.173-6C>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000227266.10	NP_001805.4
CTSC	NM_001114173.3 linkuse as main transcript	c.173-6C>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NP_001107645.1
CTSC	NM_148170.5 linkuse as main transcript	c.173-6C>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NP_680475.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTSC	ENST00000227266.10 linkuse as main transcript	c.173-6C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001814.6	ENSP00000227266	P1	P53634-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

108102

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000921

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000406

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000883

AC:

AN:

1120634

Hom.:

Cov.:

AF XY:

0.0000743

AC XY:

AN XY:

565312

show subpopulations

Gnomad4 AFR exome

AF:

0.0000772

Gnomad4 AMR exome

AF:

0.0000277

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000415

Gnomad4 FIN exome

AF:

0.0000233

Gnomad4 NFE exome

AF:

0.0000995

Gnomad4 OTH exome

AF:

0.000189

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000277

AC:

AN:

108142

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

52116

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000920

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000406

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

3.2

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000063

dbscSNV1_RF

Benign

0.046

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over