rs10369

Positions:

• chr20-58995401-C-T

Variant summary

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

The NM_001336.4(CTSZ):​c.*248G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 430,346 control chromosomes in the GnomAD database, including 19,650 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 0.29 (6739 hom., cov: 31)
  • Exomes 𝑓: 0.29 (12911 hom.)
• Consequence: CTSZ NM_001336.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.68

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]

CTSZ (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTSZ	NM_001336.4	c.*248G>A		3_prime_UTR_variant	6/6	ENST00000217131.6	NP_001327.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTSZ	ENST00000217131.6	c.*248G>A		3_prime_UTR_variant	6/6	1	NM_001336.4	ENSP00000217131.5

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44306 AN: 151890 Hom.: 6738 Cov.: 31

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.277

GnomAD4 exome AF: 0.293 AC: 81608 AN: 278338 Hom.: 12911 Cov.: 2 AF XY: 0.294 AC XY: 42002 AN XY: 143050

Gnomad4 AFR exome AF: 0.244

Gnomad4 AMR exome AF: 0.233

Gnomad4 ASJ exome AF: 0.348

Gnomad4 EAS exome AF: 0.0991

Gnomad4 SAS exome AF: 0.294

Gnomad4 FIN exome AF: 0.326

Gnomad4 NFE exome AF: 0.316

Gnomad4 OTH exome AF: 0.294

GnomAD4 genome AF: 0.292 AC: 44323 AN: 152008 Hom.: 6739 Cov.: 31 AF XY: 0.290 AC XY: 21503 AN XY: 74274

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.332

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.275

Alfa AF: 0.307 Hom.: 7379

Bravo AF: 0.282

Asia WGS AF: 0.246 AC: 855 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.32
DANN	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs10369; hg19: chr20-57570456;