20-58997620-A-G

Position:

• chr20-58997620-A-G

Variant summary

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

The NM_001336.4(CTSZ):​c.621T>C​(p.Tyr207Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.997 in 1,600,156 control chromosomes in the GnomAD database, including 795,697 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 1.0 (75804 hom., cov: 30)
  • Exomes 𝑓: 1.0 (719893 hom.)
• Consequence: CTSZ NM_001336.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=0.032 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTSZ	NM_001336.4	c.621T>C	p.Tyr207Tyr	synonymous_variant	4/6	ENST00000217131.6	NP_001327.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTSZ	ENST00000217131.6	c.621T>C	p.Tyr207Tyr	synonymous_variant	4/6	1	NM_001336.4	ENSP00000217131.5

Frequencies

GnomAD3 genomes AF: 0.998 AC: 151816 AN: 152146 Hom.: 75745 Cov.: 30

Gnomad AFR AF: 0.999

Gnomad AMI AF: 1.00

Gnomad AMR AF: 1.00

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 0.997

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.996

Gnomad OTH AF: 0.999

GnomAD3 exomes AF: 0.998 AC: 240276 AN: 240750 Hom.: 119904 AF XY: 0.998 AC XY: 130192 AN XY: 130440

Gnomad AFR exome AF: 0.999

Gnomad AMR exome AF: 1.00

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 1.00

Gnomad FIN exome AF: 0.997

Gnomad NFE exome AF: 0.997

Gnomad OTH exome AF: 0.997

GnomAD4 exome AF: 0.997 AC: 1443826 AN: 1447892 Hom.: 719893 Cov.: 51 AF XY: 0.997 AC XY: 717338 AN XY: 719264

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.997

Gnomad4 NFE exome AF: 0.997

Gnomad4 OTH exome AF: 0.998

GnomAD4 genome AF: 0.998 AC: 151934 AN: 152264 Hom.: 75804 Cov.: 30 AF XY: 0.998 AC XY: 74288 AN XY: 74452

Gnomad4 AFR AF: 0.999

Gnomad4 AMR AF: 1.00

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 0.997

Gnomad4 NFE AF: 0.996

Gnomad4 OTH AF: 0.999

Alfa AF: 0.997 Hom.: 32208

Bravo AF: 0.998

Asia WGS AF: 1.00 AC: 3478 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.26
DANN	Benign	0.43

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: rs163785; hg19: chr20-57572675;