20-59000539-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.487+926G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 152,090 control chromosomes in the GnomAD database, including 40,031 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 0.72 (40031 hom., cov: 33)
• Consequence: CTSZ NM_001336.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTSZ	NM_001336.4	c.487+926G>A		intron_variant		ENST00000217131.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTSZ	ENST00000217131.6	c.487+926G>A		intron_variant		1	NM_001336.4	P1

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109951 AN: 151972 Hom.: 39993 Cov.: 33

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.804

Gnomad AMR AF: 0.750

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.796

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.719

Gnomad OTH AF: 0.725

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.724 AC: 110045 AN: 152090 Hom.: 40031 Cov.: 33 AF XY: 0.722 AC XY: 53640 AN XY: 74340

Gnomad4 AFR AF: 0.708

Gnomad4 AMR AF: 0.750

Gnomad4 ASJ AF: 0.709

Gnomad4 EAS AF: 0.909

Gnomad4 SAS AF: 0.796

Gnomad4 FIN AF: 0.650

Gnomad4 NFE AF: 0.719

Gnomad4 OTH AF: 0.724

Alfa AF: 0.717 Hom.: 37950

Bravo AF: 0.731

Asia WGS AF: 0.848 AC: 2948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.1
Dann	Benign	0.43

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: rs163790; hg19: chr20-57575594;