chr20-58996763-G-C
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_001336.4(CTSZ):c.677C>G(p.Thr226Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00306 in 1,614,156 control chromosomes in the GnomAD database, including 144 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.016 ( 71 hom., cov: 30)
Exomes 𝑓: 0.0017 ( 73 hom. )
Consequence
CTSZ
NM_001336.4 missense
NM_001336.4 missense
Scores
2
16
Clinical Significance
Conservation
PhyloP100: 0.814
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0060233474).
BP6
?
Variant 20-58996763-G-C is Benign according to our data. Variant chr20-58996763-G-C is described in ClinVar as [Benign]. Clinvar id is 785663.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0551 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CTSZ | NM_001336.4 | c.677C>G | p.Thr226Ser | missense_variant | 5/6 | ENST00000217131.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTSZ | ENST00000217131.6 | c.677C>G | p.Thr226Ser | missense_variant | 5/6 | 1 | NM_001336.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0163 AC: 2476AN: 152188Hom.: 72 Cov.: 30
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00416 AC: 1047AN: 251456Hom.: 34 AF XY: 0.00314 AC XY: 427AN XY: 135900
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GnomAD4 exome AF: 0.00168 AC: 2457AN: 1461850Hom.: 73 Cov.: 33 AF XY: 0.00144 AC XY: 1044AN XY: 727230
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GnomAD4 genome ? AF: 0.0163 AC: 2482AN: 152306Hom.: 71 Cov.: 30 AF XY: 0.0155 AC XY: 1158AN XY: 74478
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ESP6500AA
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225
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601
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3478
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | May 09, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Uncertain
D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Uncertain
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Gain of glycosylation at T226 (P = 0.013);
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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