Genetic Variant CTSZ:p.Arg189Arg (chr20-58997674-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001336.4(CTSZ):c.567G>A(p.Arg189Arg) 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

Publications

5 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
CTSZ	NM_001336.4 link	c.567G>A	p.Arg189Arg	synonymous_variant	Exon 4 of 6	ENST00000217131.6	NP_001327.2	Q9UBR2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTSZ	ENST00000217131.6 link	c.567G>A	p.Arg189Arg	synonymous_variant	Exon 4 of 6	1	NM_001336.4	ENSP00000217131.5		Q9UBR2

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

GnomAD2 exomes

AF:

0.00649

AC:

1604

AN:

247168

AF XY:

0.00643

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 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

African (AFR)

AF:

0.00141

AC:

AN:

33386

American (AMR)

AF:

0.00280

AC:

123

AN:

43996

Ashkenazi Jewish (ASJ)

AF:

0.0258

AC:

673

AN:

26098

East Asian (EAS)

AF:

0.000101

AC:

AN:

39522

South Asian (SAS)

AF:

0.00108

AC:

AN:

85028

European-Finnish (FIN)

AF:

0.00116

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00486

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00926

AC:

10275

AN:

1110098

Other (OTH)

AF:

0.00817

AC:

492

AN:

60240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

601

1202

1803

2404

3005

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

390

780

1170

1560

1950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00649

AC:

989

AN:

152330

Hom.:

Cov.:

AF XY:

0.00618

AC XY:

460

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.00192

AC:

AN:

41586

American (AMR)

AF:

0.00523

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0253

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00104

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00132

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00967

AC:

658

AN:

68034

Other (OTH)

AF:

0.00711

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

134

178

223

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Jul 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CTSZ: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

1.2

(source)

DANN

Benign

0.81

PhyloP100

-0.26

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=91/9

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over