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GeneBe

20-58997674-C-T

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

2

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.263 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 6 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CTSZNM_001336.4 linkuse as main transcriptc.567G>A p.Arg189= synonymous_variant 4/6 ENST00000217131.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CTSZENST00000217131.6 linkuse as main transcriptc.567G>A p.Arg189= synonymous_variant 4/61 NM_001336.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00650
AC:
989
AN:
152212
Hom.:
6
Cov.:
32
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.:
15
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.:
62
Cov.:
34
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00649
AC:
989
AN:
152330
Hom.:
6
Cov.:
32
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.:
5
Bravo
AF:
0.00720
Asia WGS
AF:
0.00202
AC:
7
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 submitterclinical testingCeGaT Center for Human Genetics TuebingenJul 01, 2022CTSZ: 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.

Other links and lift over

dbSNP: rs11540881; hg19: chr20-57572729; COSMIC: COSV99413799; COSMIC: COSV99413799; API