20-58996708-A-G

Position:

• chr20-58996708-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000217131.6(CTSZ):​c.732T>C​(p.Ser244=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 1,613,790 control chromosomes in the GnomAD database, including 334,683 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 0.66 (33569 hom., cov: 32)
  • Exomes 𝑓: 0.64 (301114 hom.)
• Consequence: CTSZ ENST00000217131.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.83

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-3.83 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTSZ	NM_001336.4	c.732T>C	p.Ser244=	synonymous_variant	5/6	ENST00000217131.6	NP_001327.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTSZ	ENST00000217131.6	c.732T>C	p.Ser244=	synonymous_variant	5/6	1	NM_001336.4	ENSP00000217131	P1

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100565 AN: 151986 Hom.: 33539 Cov.: 32

Gnomad AFR AF: 0.724

Gnomad AMI AF: 0.712

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.634

GnomAD3 exomes AF: 0.635 AC: 159785 AN: 251458 Hom.: 51360 AF XY: 0.635 AC XY: 86361 AN XY: 135896

Gnomad AFR exome AF: 0.727

Gnomad AMR exome AF: 0.562

Gnomad ASJ exome AF: 0.614

Gnomad EAS exome AF: 0.785

Gnomad SAS exome AF: 0.642

Gnomad FIN exome AF: 0.584

Gnomad NFE exome AF: 0.631

Gnomad OTH exome AF: 0.621

GnomAD4 exome AF: 0.641 AC: 936527 AN: 1461686 Hom.: 301114 Cov.: 47 AF XY: 0.640 AC XY: 465458 AN XY: 727156

Gnomad4 AFR exome AF: 0.726

Gnomad4 AMR exome AF: 0.570

Gnomad4 ASJ exome AF: 0.611

Gnomad4 EAS exome AF: 0.801

Gnomad4 SAS exome AF: 0.645

Gnomad4 FIN exome AF: 0.593

Gnomad4 NFE exome AF: 0.638

Gnomad4 OTH exome AF: 0.644

GnomAD4 genome AF: 0.662 AC: 100660 AN: 152104 Hom.: 33569 Cov.: 32 AF XY: 0.658 AC XY: 48932 AN XY: 74350

Gnomad4 AFR AF: 0.724

Gnomad4 AMR AF: 0.606

Gnomad4 ASJ AF: 0.609

Gnomad4 EAS AF: 0.788

Gnomad4 SAS AF: 0.653

Gnomad4 FIN AF: 0.595

Gnomad4 NFE AF: 0.641

Gnomad4 OTH AF: 0.633

Alfa AF: 0.635 Hom.: 49941

Bravo AF: 0.667

Asia WGS AF: 0.692 AC: 2409 AN: 3478

EpiCase AF: 0.623

EpiControl AF: 0.622

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.13
DANN	Benign	0.50

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

Other links and lift over

dbSNP: rs9760; hg19: chr20-57571763;