rs3787492

Positions:

• chr20-58995799-G-A
• chr20-58995799-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001336.4(CTSZ):​c.802-40C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 1,576,296 control chromosomes in the GnomAD database, including 109,933 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.35 (9637 hom., cov: 31)
  • Exomes 𝑓: 0.37 (100296 hom.)
• Consequence: CTSZ NM_001336.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.254

Genes affected

CTSZ (HGNC:2547): (cathepsin Z) The protein encoded by this gene is a lysosomal cysteine proteinase and member of the peptidase C1 family. It exhibits both carboxy-monopeptidase and carboxy-dipeptidase activities. The encoded protein has also been known as cathepsin X and cathepsin P. This gene is expressed ubiquitously in cancer cell lines and primary tumors and, like other members of this family, may be involved in tumorigenesis. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTSZ	NM_001336.4	c.802-40C>T		intron_variant		ENST00000217131.6	NP_001327.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTSZ	ENST00000217131.6	c.802-40C>T		intron_variant		1	NM_001336.4	ENSP00000217131.5

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52797 AN: 151798 Hom.: 9634 Cov.: 31

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.328

GnomAD3 exomes AF: 0.339 AC: 83252 AN: 245264 Hom.: 15064 AF XY: 0.342 AC XY: 45488 AN XY: 132926

Gnomad AFR exome AF: 0.289

Gnomad AMR exome AF: 0.241

Gnomad ASJ exome AF: 0.337

Gnomad EAS exome AF: 0.181

Gnomad SAS exome AF: 0.276

Gnomad FIN exome AF: 0.491

Gnomad NFE exome AF: 0.394

Gnomad OTH exome AF: 0.345

GnomAD4 exome AF: 0.370 AC: 527549 AN: 1424378 Hom.: 100296 Cov.: 24 AF XY: 0.368 AC XY: 261702 AN XY: 710566

Gnomad4 AFR exome AF: 0.288

Gnomad4 AMR exome AF: 0.244

Gnomad4 ASJ exome AF: 0.341

Gnomad4 EAS exome AF: 0.172

Gnomad4 SAS exome AF: 0.279

Gnomad4 FIN exome AF: 0.481

Gnomad4 NFE exome AF: 0.389

Gnomad4 OTH exome AF: 0.351

GnomAD4 genome AF: 0.348 AC: 52812 AN: 151918 Hom.: 9637 Cov.: 31 AF XY: 0.350 AC XY: 25986 AN XY: 74236

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.494

Gnomad4 NFE AF: 0.391

Gnomad4 OTH AF: 0.329

Alfa AF: 0.325 Hom.: 2169

Bravo AF: 0.329

Asia WGS AF: 0.218 AC: 762 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.78
DANN	Benign	0.77

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

LitVar

Other links and lift over

dbSNP: rs3787492; hg19: chr20-57570854; COSMIC: COSV53883973; COSMIC: COSV53883973;