Genetic Variant CTSZ:c.*466T>G (chr20-58995183-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000681011(CTSZ):c.*466T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CTSZ
ENST00000681011 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.793

Variant links:

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 links:

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]

NELFCD links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NELFCD	NM_198976.4 link	c.*507A>C		downstream_gene_variant		ENST00000652272.2	NP_945327.3	Q8IXH7-4H0UI80
CTSZ	NM_001336.4 link	c.*466T>G		downstream_gene_variant		ENST00000217131.6	NP_001327.2	Q9UBR2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NELFCD	ENST00000652272.2 link	c.*507A>C		downstream_gene_variant			NM_198976.4	ENSP00000499018.1		Q8IXH7-4
CTSZ	ENST00000217131.6 link	c.*466T>G		downstream_gene_variant		1	NM_001336.4	ENSP00000217131.5		Q9UBR2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

17416

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

8810

African (AFR)

AF:

0.00

AC:

AN:

514

American (AMR)

AF:

0.00

AC:

AN:

1494

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

518

East Asian (EAS)

AF:

0.00

AC:

AN:

638

South Asian (SAS)

AF:

0.00

AC:

AN:

1394

European-Finnish (FIN)

AF:

0.00

AC:

AN:

580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

11272

Other (OTH)

AF:

0.00

AC:

AN:

962

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

35261

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.14

DANN

Benign

0.44

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over