Variant rs11540881 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001336.4(CTSZ):c.567G>A(p.Arg189=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00794 in 1,609,850 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0065 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0081 ( 62 hom. )

Consequence

CTSZ
NM_001336.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.263

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 20-58997674-C-T is Benign according to our data. Variant chr20-58997674-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2652451.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.263 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTSZ	NM_001336.4 linkuse as main transcript	c.567G>A	p.Arg189=	synonymous_variant	4/6	ENST00000217131.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTSZ	ENST00000217131.6 linkuse as main transcript	c.567G>A	p.Arg189=	synonymous_variant	4/6	1	NM_001336.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00650

AC:

989

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00193

Gnomad AMI

AF:

0.0527

Gnomad AMR

AF:

0.00524

Gnomad ASJ

AF:

0.0253

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00967

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00649

AC:

1604

AN:

247168

Hom.:

AF XY:

0.00643

AC XY:

859

AN XY:

133646

show subpopulations

Gnomad AFR exome

AF:

0.000928

Gnomad AMR exome

AF:

0.00222

Gnomad ASJ exome

AF:

0.0293

Gnomad EAS exome

AF:

0.000275

Gnomad SAS exome

AF:

0.00111

Gnomad FIN exome

AF:

0.00111

Gnomad NFE exome

AF:

0.00994

Gnomad OTH exome

AF:

0.00673

GnomAD4 exome

AF:

0.00809

AC:

11796

AN:

1457520

Hom.:

Cov.:

AF XY:

0.00795

AC XY:

5763

AN XY:

724832

show subpopulations

Gnomad4 AFR exome

AF:

0.00141

Gnomad4 AMR exome

AF:

0.00280

Gnomad4 ASJ exome

AF:

0.0258

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00108

Gnomad4 FIN exome

AF:

0.00116

Gnomad4 NFE exome

AF:

0.00926

Gnomad4 OTH exome

AF:

0.00817

GnomAD4 genome

AF:

0.00649

AC:

989

AN:

152330

Hom.:

Cov.:

AF XY:

0.00618

AC XY:

460

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00192

Gnomad4 AMR

AF:

0.00523

Gnomad4 ASJ

AF:

0.0253

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.00967

Gnomad4 OTH

AF:

0.00711

Alfa

AF:

0.00988

Hom.:

Bravo

AF:

0.00720

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

CTSZ: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

1.2

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over