rs13720

Positions:

• chr20-58995513-G-A
• chr20-58995513-G-C

Variant summary

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

The NM_001336.4(CTSZ):​c.*136C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.815 in 703,528 control chromosomes in the GnomAD database, including 234,419 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 0.83 (51985 hom., cov: 31)
  • Exomes 𝑓: 0.81 (182434 hom.)
• Consequence: CTSZ NM_001336.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.71

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTSZ	NM_001336.4	c.*136C>T		3_prime_UTR_variant	6/6	ENST00000217131.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTSZ	ENST00000217131.6	c.*136C>T		3_prime_UTR_variant	6/6	1	NM_001336.4	P1

Frequencies

GnomAD3 genomes AF: 0.825 AC: 125406 AN: 151966 Hom.: 51924 Cov.: 31

Gnomad AFR AF: 0.865

Gnomad AMI AF: 0.863

Gnomad AMR AF: 0.760

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.822

Gnomad FIN AF: 0.852

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.811

Gnomad OTH AF: 0.798

GnomAD4 exome AF: 0.813 AC: 448099 AN: 551444 Hom.: 182434 Cov.: 7 AF XY: 0.813 AC XY: 235335 AN XY: 289632

Gnomad4 AFR exome AF: 0.860

Gnomad4 AMR exome AF: 0.731

Gnomad4 ASJ exome AF: 0.805

Gnomad4 EAS exome AF: 0.874

Gnomad4 SAS exome AF: 0.818

Gnomad4 FIN exome AF: 0.838

Gnomad4 NFE exome AF: 0.808

Gnomad4 OTH exome AF: 0.812

GnomAD4 genome AF: 0.825 AC: 125525 AN: 152084 Hom.: 51985 Cov.: 31 AF XY: 0.827 AC XY: 61459 AN XY: 74336

Gnomad4 AFR AF: 0.865

Gnomad4 AMR AF: 0.759

Gnomad4 ASJ AF: 0.803

Gnomad4 EAS AF: 0.872

Gnomad4 SAS AF: 0.823

Gnomad4 FIN AF: 0.852

Gnomad4 NFE AF: 0.811

Gnomad4 OTH AF: 0.799

Alfa AF: 0.812 Hom.: 16407

Bravo AF: 0.820

Asia WGS AF: 0.814 AC: 2832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.11
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs13720; hg19: chr20-57570568;