chr20-58995401-C-T

Variant names:

• chr20-58995401-C-T
• rs10369
• NM_001336.4:c.*248G>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.*248G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 430,346 control chromosomes in the GnomAD database, including 19,650 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 0.29 (6739 hom., cov: 31)
  • Exomes 𝑓: 0.29 (12911 hom.)
• Consequence: CTSZ NM_001336.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.68
• Publications: 20 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.319 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.*248G>A		3_prime_UTR	Exon 6 of 6	NP_001327.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTSZ	ENST00000217131.6	TSL:1 MANE Select	c.*248G>A		3_prime_UTR	Exon 6 of 6	ENSP00000217131.5	Q9UBR2
	CTSZ	ENST00000680995.1		c.*248G>A		3_prime_UTR	Exon 7 of 7	ENSP00000505169.1	A0A7P0T8I6
	CTSZ	ENST00000680738.1		c.*405G>A		3_prime_UTR	Exon 7 of 7	ENSP00000506672.1	A0A7P0TBM7

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44306 AN: 151890 Hom.: 6738 Cov.: 31

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.277

GnomAD4 exome AF: 0.293 AC: 81608 AN: 278338 Hom.: 12911 Cov.: 2 AF XY: 0.294 AC XY: 42002 AN XY: 143050

African (AFR) AF: 0.244 AC: 1918 AN: 7850

American (AMR) AF: 0.233 AC: 2097 AN: 9008

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 3407 AN: 9804

East Asian (EAS) AF: 0.0991 AC: 2175 AN: 21956

South Asian (SAS) AF: 0.294 AC: 4318 AN: 14668

European-Finnish (FIN) AF: 0.326 AC: 6923 AN: 21268

Middle Eastern (MID) AF: 0.256 AC: 365 AN: 1424

European-Non Finnish (NFE) AF: 0.316 AC: 55179 AN: 174598

Other (OTH) AF: 0.294 AC: 5226 AN: 17762

GnomAD4 genome AF: 0.292 AC: 44323 AN: 152008 Hom.: 6739 Cov.: 31 AF XY: 0.290 AC XY: 21503 AN XY: 74274

African (AFR) AF: 0.253 AC: 10468 AN: 41448

American (AMR) AF: 0.247 AC: 3766 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1256 AN: 3472

East Asian (EAS) AF: 0.187 AC: 969 AN: 5172

South Asian (SAS) AF: 0.294 AC: 1420 AN: 4822

European-Finnish (FIN) AF: 0.332 AC: 3496 AN: 10540

Middle Eastern (MID) AF: 0.240 AC: 70 AN: 292

European-Non Finnish (NFE) AF: 0.322 AC: 21898 AN: 67966

Other (OTH) AF: 0.275 AC: 581 AN: 2112

Alfa AF: 0.304 Hom.: 9403

Bravo AF: 0.282

Asia WGS AF: 0.246 AC: 855 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.32
DANN	Benign	0.53
PhyloP100		-2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs10369; hg19: chr20-57570456;