20-58996708-A-G

Variant names:

• chr20-58996708-A-G
• rs9760
• NM_001336.4:c.732T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001336.4(CTSZ):​c.732T>C​(p.Ser244Ser) 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 NM_001336.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.83
• Publications: 36 publications found

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

Our verdict: Benign. The variant received -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.

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.732T>C	p.Ser244Ser	synonymous	Exon 5 of 6	NP_001327.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTSZ	ENST00000217131.6	TSL:1 MANE Select	c.732T>C	p.Ser244Ser	synonymous	Exon 5 of 6	ENSP00000217131.5
	CTSZ	ENST00000503833.7	TSL:1	n.732T>C		non_coding_transcript_exon	Exon 5 of 5	ENSP00000506414.1
	CTSZ	ENST00000680995.1		c.825T>C	p.Ser275Ser	synonymous	Exon 6 of 7	ENSP00000505169.1

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

GnomAD2 exomes AF: 0.635 AC: 159785 AN: 251458 AF XY: 0.635

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 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

African (AFR) AF: 0.726 AC: 24319 AN: 33480

American (AMR) AF: 0.570 AC: 25509 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 15965 AN: 26136

East Asian (EAS) AF: 0.801 AC: 31789 AN: 39700

South Asian (SAS) AF: 0.645 AC: 55620 AN: 86258

European-Finnish (FIN) AF: 0.593 AC: 31658 AN: 53418

Middle Eastern (MID) AF: 0.577 AC: 3328 AN: 5768

European-Non Finnish (NFE) AF: 0.638 AC: 709452 AN: 1111816

Other (OTH) AF: 0.644 AC: 38887 AN: 60386

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

African (AFR) AF: 0.724 AC: 30046 AN: 41506

American (AMR) AF: 0.606 AC: 9247 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 2113 AN: 3472

East Asian (EAS) AF: 0.788 AC: 4074 AN: 5170

South Asian (SAS) AF: 0.653 AC: 3142 AN: 4814

European-Finnish (FIN) AF: 0.595 AC: 6282 AN: 10556

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.641 AC: 43619 AN: 68000

Other (OTH) AF: 0.633 AC: 1339 AN: 2114

Alfa AF: 0.638 Hom.: 61370

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.13
DANN	Benign	0.50
PhyloP100		-3.8
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9760; hg19: chr20-57571763; COSMIC: COSV107249523; COSMIC: COSV107249523;