dbSNP rs13720: 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTSZ	NM_001336.4 link	c.*136C>T		3_prime_UTR_variant	Exon 6 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.*136C>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_001336.4	ENSP00000217131.5		Q9UBR2

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over