11-65879879-TGCCTCCTG-T

Position:

• chr11-65879879-TGCCTCCTG-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001335.4(CTSW):​c.29_36del​(p.Leu10ProfsTer15) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00372 in 1,613,784 control chromosomes in the GnomAD database, including 16 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0038 (14 hom.)
• Consequence: CTSW NM_001335.4 frameshift
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.56

Genes affected

CTSW (HGNC:2546): (cathepsin W) The protein encoded by this gene, a member of the peptidase C1 family, is a cysteine proteinase that may have a specific function in the mechanism or regulation of T-cell cytolytic activity. The encoded protein is found associated with the membrane inside the endoplasmic reticulum of natural killer and cytotoxic T-cells. Expression of this gene is up-regulated by interleukin-2. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 11-65879879-TGCCTCCTG-T is Benign according to our data. Variant chr11-65879879-TGCCTCCTG-T is described in ClinVar as [Likely_benign]. Clinvar id is 2641975.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTSW	NM_001335.4	c.29_36del	p.Leu10ProfsTer15	frameshift_variant	1/10	ENST00000307886.8	NP_001326.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTSW	ENST00000307886.8	c.29_36del	p.Leu10ProfsTer15	frameshift_variant	1/10	1	NM_001335.4	ENSP00000311300	P1

Frequencies

GnomAD3 genomes AF: 0.00306 AC: 466 AN: 152208 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000844

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00706

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00429

Gnomad OTH AF: 0.00623

GnomAD3 exomes AF: 0.00307 AC: 764 AN: 248856 Hom.: 2 AF XY: 0.00303 AC XY: 409 AN XY: 134866

Gnomad AFR exome AF: 0.000932

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.00210

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00125

Gnomad FIN exome AF: 0.00751

Gnomad NFE exome AF: 0.00406

Gnomad OTH exome AF: 0.00412

GnomAD4 exome AF: 0.00379 AC: 5537 AN: 1461458 Hom.: 14 AF XY: 0.00385 AC XY: 2797 AN XY: 726992

Gnomad4 AFR exome AF: 0.000478

Gnomad4 AMR exome AF: 0.00157

Gnomad4 ASJ exome AF: 0.00352

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00116

Gnomad4 FIN exome AF: 0.00730

Gnomad4 NFE exome AF: 0.00423

Gnomad4 OTH exome AF: 0.00278

GnomAD4 genome AF: 0.00306 AC: 466 AN: 152326 Hom.: 2 Cov.: 33 AF XY: 0.00315 AC XY: 235 AN XY: 74490

Gnomad4 AFR AF: 0.000842

Gnomad4 AMR AF: 0.00203

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00706

Gnomad4 NFE AF: 0.00429

Gnomad4 OTH AF: 0.00616

Alfa AF: 0.00371 Hom.: 1

Bravo AF: 0.00248

EpiCase AF: 0.00393

EpiControl AF: 0.00439

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

CTSW: BS2 -

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: rs532284219; hg19: chr11-65647350;