20-58997654-A-G
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The ENST00000217131.6(CTSZ):āc.587T>Cā(p.Leu196Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00711 in 1,608,464 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0050 ( 6 hom., cov: 32)
Exomes š: 0.0073 ( 53 hom. )
Consequence
CTSZ
ENST00000217131.6 missense
ENST00000217131.6 missense
Scores
1
10
8
Clinical Significance
Conservation
PhyloP100: 7.49
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.011101931).
BP6
Variant 20-58997654-A-G is Benign according to our data. Variant chr20-58997654-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 779289.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAd4 at 6 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CTSZ | NM_001336.4 | c.587T>C | p.Leu196Pro | missense_variant | 4/6 | ENST00000217131.6 | NP_001327.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CTSZ | ENST00000217131.6 | c.587T>C | p.Leu196Pro | missense_variant | 4/6 | 1 | NM_001336.4 | ENSP00000217131 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00500 AC: 761AN: 152150Hom.: 6 Cov.: 32
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GnomAD3 exomes AF: 0.00488 AC: 1202AN: 246222Hom.: 4 AF XY: 0.00513 AC XY: 683AN XY: 133184
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GnomAD4 exome AF: 0.00733 AC: 10679AN: 1456196Hom.: 53 Cov.: 35 AF XY: 0.00727 AC XY: 5263AN XY: 724036
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GnomAD4 genome AF: 0.00500 AC: 761AN: 152268Hom.: 6 Cov.: 32 AF XY: 0.00501 AC XY: 373AN XY: 74446
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 17, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2024 | CTSZ: BP4, BS2 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at