20-58995183-A-G

Position:

• chr20-58995183-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000681011.1(CTSZ):​c.*466T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 169,292 control chromosomes in the GnomAD database, including 32,030 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 0.61 (28821 hom., cov: 31)
  • Exomes 𝑓: 0.59 (3209 hom.)
• Consequence: CTSZ ENST00000681011.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.793

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:):

NELFCD (HGNC:15934): (negative elongation factor complex member C/D) The NELF complex of proteins interacts with the DSIF protein complex to repress transcriptional elongation by RNA polymerase II. The protein encoded by this gene is an essential part of the NELF complex. Alternative translation initiation site usage results in the formation of two isoforms with different N-termini. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.58995183A>G		intergenic_region
CTSZ	NM_001336.4	c.*466T>C		downstream_gene_variant		ENST00000217131.6	NP_001327.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTSZ	ENST00000217131.6	c.*466T>C		downstream_gene_variant		1	NM_001336.4	ENSP00000217131.5

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93123 AN: 151818 Hom.: 28813 Cov.: 31

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.712

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.599

GnomAD4 exome AF: 0.589 AC: 10227 AN: 17356 Hom.: 3209 Cov.: 0 AF XY: 0.583 AC XY: 5122 AN XY: 8782

Gnomad4 AFR exome AF: 0.518

Gnomad4 AMR exome AF: 0.523

Gnomad4 ASJ exome AF: 0.588

Gnomad4 EAS exome AF: 0.810

Gnomad4 SAS exome AF: 0.600

Gnomad4 FIN exome AF: 0.523

Gnomad4 NFE exome AF: 0.594

Gnomad4 OTH exome AF: 0.563

GnomAD4 genome AF: 0.613 AC: 93180 AN: 151936 Hom.: 28821 Cov.: 31 AF XY: 0.610 AC XY: 45327 AN XY: 74246

Gnomad4 AFR AF: 0.558

Gnomad4 AMR AF: 0.588

Gnomad4 ASJ AF: 0.610

Gnomad4 EAS AF: 0.788

Gnomad4 SAS AF: 0.647

Gnomad4 FIN AF: 0.593

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.599

Alfa AF: 0.343 Hom.: 430

Bravo AF: 0.612

Asia WGS AF: 0.673 AC: 2345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.14
DANN	Benign	0.36

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs448943; hg19: chr20-57570238;