Genetic Variant CTSZ:c.*136C>T (chr20-58995513-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001336.4(CTSZ):c.*136C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.815 in 703,528 control chromosomes in the GnomAD database, including 234,419 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 0.83 ( 51985 hom., cov: 31)

Exomes 𝑓: 0.81 ( 182434 hom. )

Consequence

CTSZ
NM_001336.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.71

Publications

18 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001336.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTSZ	NM_001336.4	MANE Select	c.*136C>T		3_prime_UTR	Exon 6 of 6	NP_001327.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CTSZ	ENST00000217131.6	TSL:1 MANE Select	c.*136C>T	3_prime_UTR	Exon 6 of 6	ENSP00000217131.5
CTSZ	ENST00000488395.2	TSL:2	n.2870C>T	non_coding_transcript_exon	Exon 4 of 4
CTSZ	ENST00000679391.1		n.1957C>T	non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes

AF:

0.825

AC:

125406

AN:

151966

Hom.:

51924

Cov.:

show subpopulations

Gnomad AFR

AF:

0.865

Gnomad AMI

AF:

0.863

Gnomad AMR

AF:

0.760

Gnomad ASJ

AF:

0.803

Gnomad EAS

AF:

0.872

Gnomad SAS

AF:

0.822

Gnomad FIN

AF:

0.852

Gnomad MID

AF:

0.687

Gnomad NFE

AF:

0.811

Gnomad OTH

AF:

0.798

GnomAD4 exome

AF:

0.813

AC:

448099

AN:

551444

Hom.:

182434

Cov.:

AF XY:

0.813

AC XY:

235335

AN XY:

289632

show subpopulations

African (AFR)

AF:

0.860

AC:

12999

AN:

15122

American (AMR)

AF:

0.731

AC:

19230

AN:

26308

Ashkenazi Jewish (ASJ)

AF:

0.805

AC:

12447

AN:

15454

East Asian (EAS)

AF:

0.874

AC:

27857

AN:

31884

South Asian (SAS)

AF:

0.818

AC:

41880

AN:

51228

European-Finnish (FIN)

AF:

0.838

AC:

33566

AN:

40076

Middle Eastern (MID)

AF:

0.755

AC:

2557

AN:

3386

European-Non Finnish (NFE)

AF:

0.808

AC:

273675

AN:

338562

Other (OTH)

AF:

0.812

AC:

23888

AN:

29424

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

4064

8128

12191

16255

20319

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2400

4800

7200

9600

12000

<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:

0.825

AC:

125525

AN:

152084

Hom.:

51985

Cov.:

AF XY:

0.827

AC XY:

61459

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.865

AC:

35862

AN:

41462

American (AMR)

AF:

0.759

AC:

11592

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.803

AC:

2784

AN:

3466

East Asian (EAS)

AF:

0.872

AC:

4504

AN:

5166

South Asian (SAS)

AF:

0.823

AC:

3965

AN:

4818

European-Finnish (FIN)

AF:

0.852

AC:

9025

AN:

10598

Middle Eastern (MID)

AF:

0.701

AC:

206

AN:

294

European-Non Finnish (NFE)

AF:

0.811

AC:

55118

AN:

67996

Other (OTH)

AF:

0.799

AC:

1684

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1103

2205

3308

4410

5513

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

884

1768

2652

3536

4420

<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:

0.812

Hom.:

28529

Bravo

AF:

0.820

Asia WGS

AF:

0.814

AC:

2832

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.11

(source)

DANN

Benign

0.75

PhyloP100

-2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Mutation Taster

=100/0

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over