20-59000539-C-T

Variant names:

• chr20-59000539-C-T
• rs163790
• NM_001336.4:c.487+926G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001336.4(CTSZ):​c.487+926G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 152,090 control chromosomes in the GnomAD database, including 40,031 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 0.72 (40031 hom., cov: 33)
• Consequence: CTSZ NM_001336.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.887 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTSZ	NM_001336.4	MANE Select	c.487+926G>A		intron	N/A	NP_001327.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTSZ	ENST00000217131.6	TSL:1 MANE Select	c.487+926G>A		intron	N/A	ENSP00000217131.5	Q9UBR2
	CTSZ	ENST00000503833.7	TSL:1	n.487+926G>A		intron	N/A	ENSP00000506414.1	A0A7P0TB41
	CTSZ	ENST00000680995.1		c.487+926G>A		intron	N/A	ENSP00000505169.1	A0A7P0T8I6

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109951 AN: 151972 Hom.: 39993 Cov.: 33

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.804

Gnomad AMR AF: 0.750

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.796

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.719

Gnomad OTH AF: 0.725

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.724 AC: 110045 AN: 152090 Hom.: 40031 Cov.: 33 AF XY: 0.722 AC XY: 53640 AN XY: 74340

African (AFR) AF: 0.708 AC: 29373 AN: 41474

American (AMR) AF: 0.750 AC: 11472 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.709 AC: 2459 AN: 3466

East Asian (EAS) AF: 0.909 AC: 4693 AN: 5164

South Asian (SAS) AF: 0.796 AC: 3843 AN: 4826

European-Finnish (FIN) AF: 0.650 AC: 6862 AN: 10564

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.719 AC: 48886 AN: 67992

Other (OTH) AF: 0.724 AC: 1529 AN: 2112

Alfa AF: 0.720 Hom.: 50010

Bravo AF: 0.731

Asia WGS AF: 0.848 AC: 2948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.43
PhyloP100		-0.29
Mutation Taster		=100/0	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: rs163790; hg19: chr20-57575594;