rs448943

Variant names:

• chr20-58995183-A-C
• rs448943
• ENST00000681011.1:c.*466T>G

Your query was ambiguous. Multiple possible variants found:

• chr20-58995183-A-C
• chr20-58995183-A-G
• chr20-58995183-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000681011.1(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 ENST00000681011.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.793
• Publications: 9 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]

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

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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000681011.1. 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
	NELFCD	NM_198976.4	MANE Select	c.*507A>C		downstream_gene	N/A	NP_945327.3	Q8IXH7-4
	CTSZ	NM_001336.4	MANE Select	c.*466T>G		downstream_gene	N/A	NP_001327.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTSZ	ENST00000681011.1		c.*466T>G		3_prime_UTR	Exon 6 of 6	ENSP00000505520.1	A0A7P0T989
	CTSZ	ENST00000681175.1		c.639-962T>G		intron	N/A	ENSP00000505215.1	A0A7P0Z469
	CTSZ	ENST00000680879.1		c.801+1456T>G		intron	N/A	ENSP00000505285.1	A0A7P0T8X2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 17416 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 8810

African (AFR) AF: 0.00 AC: 0 AN: 514

American (AMR) AF: 0.00 AC: 0 AN: 1494

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 518

East Asian (EAS) AF: 0.00 AC: 0 AN: 638

South Asian (SAS) AF: 0.00 AC: 0 AN: 1394

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 44

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 11272

Other (OTH) AF: 0.00 AC: 0 AN: 962

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 35261

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.14
DANN	Benign	0.44
PhyloP100		-0.79

Splicing

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

Other links and lift over

dbSNP: rs448943; hg19: chr20-57570238;