rs163800

chr20-59003453-T-C

Variant summary

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

The NM_001336.4(CTSZ):c.308-1809A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.839 in 152,252 control chromosomes in the GnomAD database, including 53,975 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 0.84 (53975 hom., cov: 33)
• Consequence: CTSZ NM_001336.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.433

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTSZ	NM_001336.4	c.308-1809A>G		intron_variant		ENST00000217131.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTSZ	ENST00000217131.6	c.308-1809A>G		intron_variant		1	NM_001336.4	P1

Frequencies

GnomAD3 genomes AF: 0.839 AC: 127675 AN: 152134 Hom.: 53919 Cov.: 33

Gnomad AFR AF: 0.925

Gnomad AMI AF: 0.862

Gnomad AMR AF: 0.763

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.827

Gnomad FIN AF: 0.845

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.809

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

GnomAD4 genome AF: 0.839 AC: 127788 AN: 152252 Hom.: 53975 Cov.: 33 AF XY: 0.840 AC XY: 62523 AN XY: 74436

Gnomad4 AFR AF: 0.925

Gnomad4 AMR AF: 0.763

Gnomad4 ASJ AF: 0.813

Gnomad4 EAS AF: 0.864

Gnomad4 SAS AF: 0.827

Gnomad4 FIN AF: 0.845

Gnomad4 NFE AF: 0.805

Gnomad4 OTH AF: 0.810

Alfa AF: 0.816 Hom.: 8572

Bravo AF: 0.837

Asia WGS AF: 0.822 AC: 2863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	5.5
Dann	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs163800; hg19: chr20-57578508;