Variant 20-58996763-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001336.4(CTSZ):c.677C>G(p.Thr226Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00306 in 1,614,156 control chromosomes in the GnomAD database, including 144 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.016 ( 71 hom., cov: 30)

Exomes 𝑓: 0.0017 ( 73 hom. )

Consequence

CTSZ
NM_001336.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.814

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0060233474).

BP6

Variant 20-58996763-G-C is Benign according to our data. Variant chr20-58996763-G-C is described in ClinVar as [Benign]. Clinvar id is 785663.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTSZ	NM_001336.4 linkuse as main transcript	c.677C>G	p.Thr226Ser	missense_variant	5/6	ENST00000217131.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTSZ	ENST00000217131.6 linkuse as main transcript	c.677C>G	p.Thr226Ser	missense_variant	5/6	1	NM_001336.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0163

AC:

2476

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0570

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00517

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00416

AC:

1047

AN:

251456

Hom.:

AF XY:

0.00314

AC XY:

427

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.0583

Gnomad AMR exome

AF:

0.00211

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000791

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00168

AC:

2457

AN:

1461850

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

1044

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0615

Gnomad4 AMR exome

AF:

0.00266

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000414

Gnomad4 OTH exome

AF:

0.00351

GnomAD4 genome

AF:

0.0163

AC:

2482

AN:

152306

Hom.:

Cov.:

AF XY:

0.0155

AC XY:

1158

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0570

Gnomad4 AMR

AF:

0.00516

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00992

Alfa

AF:

0.00229

Hom.:

Bravo

AF:

0.0185

ESP6500AA

AF:

0.0511

AC:

225

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00495

AC:

601

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.67

Cadd

Benign

2.5

Dann

Benign

0.87

DEOGEN2

Uncertain

0.60

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0060

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.64

MutationTaster

Benign

0.93

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.068

Sift

Benign

0.10

Sift4G

Benign

0.12

Polyphen

0.0010

Vest4

0.11

MutPred

0.48

Gain of glycosylation at T226 (P = 0.013);

MVP

0.37

MPC

0.25

ClinPred

0.0054

GERP RS

-1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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