rs163785

Variant names:

• chr20-58997620-A-C
• rs163785
• NM_001336.4:c.621T>G

Your query was ambiguous. Multiple possible variants found:

• chr20-58997620-A-C
• chr20-58997620-A-G
• chr20-58997620-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001336.4(CTSZ):​c.621T>G​(p.Tyr207*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CTSZ NM_001336.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320
• Publications: 16 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.621T>G	p.Tyr207*	stop_gained	Exon 4 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.621T>G	p.Tyr207*	stop_gained	Exon 4 of 6	ENSP00000217131.5	Q9UBR2
	CTSZ	ENST00000503833.7	TSL:1	n.621T>G		non_coding_transcript_exon	Exon 4 of 5	ENSP00000506414.1	A0A7P0TB41
	CTSZ	ENST00000680995.1		c.714T>G	p.Tyr238*	stop_gained	Exon 5 of 7	ENSP00000505169.1	A0A7P0T8I6

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1447910 Hom.: 0 Cov.: 51 AF XY: 0.00 AC XY: 0 AN XY: 719270

African (AFR) AF: 0.00 AC: 0 AN: 32970

American (AMR) AF: 0.00 AC: 0 AN: 42634

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25720

East Asian (EAS) AF: 0.00 AC: 0 AN: 39166

South Asian (SAS) AF: 0.00 AC: 0 AN: 83726

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5608

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104918

Other (OTH) AF: 0.00 AC: 0 AN: 59896

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	34
DANN	Benign	0.97
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.43	N
PhyloP100		0.032
Vest4		0.94
GERP RS		-7.3
Mutation Taster		=6/194	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs163785; hg19: chr20-57572675;