20-58997620-A-G

Variant names:

• chr20-58997620-A-G
• rs163785
• NM_001336.4:c.621T>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.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
• Publications: 16 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=-0.89).
• 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.

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.621T>C	p.Tyr207Tyr	synonymous	Exon 4 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.621T>C	p.Tyr207Tyr	synonymous	Exon 4 of 6	ENSP00000217131.5
	CTSZ	ENST00000503833.7	TSL:1	n.621T>C		non_coding_transcript_exon	Exon 4 of 5	ENSP00000506414.1
	CTSZ	ENST00000680995.1		c.714T>C	p.Tyr238Tyr	synonymous	Exon 5 of 7	ENSP00000505169.1

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

GnomAD2 exomes AF: 0.998 AC: 240276 AN: 240750 AF XY: 0.998

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 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

African (AFR) AF: 1.00 AC: 32956 AN: 32970

American (AMR) AF: 1.00 AC: 42631 AN: 42634

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 25718 AN: 25720

East Asian (EAS) AF: 1.00 AC: 39166 AN: 39166

South Asian (SAS) AF: 1.00 AC: 83724 AN: 83726

European-Finnish (FIN) AF: 0.997 AC: 53108 AN: 53270

Middle Eastern (MID) AF: 1.00 AC: 5608 AN: 5608

European-Non Finnish (NFE) AF: 0.997 AC: 1101139 AN: 1104904

Other (OTH) AF: 0.998 AC: 59776 AN: 59894

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

African (AFR) AF: 0.999 AC: 41530 AN: 41552

American (AMR) AF: 1.00 AC: 15294 AN: 15296

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5170 AN: 5170

South Asian (SAS) AF: 1.00 AC: 4818 AN: 4818

European-Finnish (FIN) AF: 0.997 AC: 10590 AN: 10618

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 0.996 AC: 67745 AN: 68020

Other (OTH) AF: 0.999 AC: 2111 AN: 2114

Alfa AF: 0.997 Hom.: 49329

Bravo AF: 0.998

Asia WGS AF: 1.00 AC: 3478 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.26
DANN	Benign	0.43
PhyloP100		0.032
Mutation Taster		=99/1	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: rs163785; hg19: chr20-57572675; COSMIC: COSV108040562; COSMIC: COSV108040562;