chr1-77723437-G-C
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_201624.3(USP33):āc.1283C>Gā(p.Ser428Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000175 in 1,603,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000020 ( 0 hom., cov: 32)
Exomes š: 0.000017 ( 0 hom. )
Consequence
USP33
NM_201624.3 missense
NM_201624.3 missense
Scores
2
15
Clinical Significance
Conservation
PhyloP100: 6.23
Genes affected
USP33 (HGNC:20059): (ubiquitin specific peptidase 33) This gene encodes a deubiquinating enzyme important in a variety of processes, including Slit-dependent cell migration and beta-2 adrenergic receptor signaling. The protein is negatively regulated through ubiquitination by von Hippel-Lindau tumor protein (VHL). Alternative splicing results in multiple transcript variants and protein isoforms. [provided by RefSeq, Jun 2012]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.05231628).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USP33 | NM_201624.3 | c.1283C>G | p.Ser428Cys | missense_variant | 12/24 | ENST00000370794.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USP33 | ENST00000370794.7 | c.1283C>G | p.Ser428Cys | missense_variant | 12/24 | 1 | NM_201624.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000198 AC: 3AN: 151844Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000612 AC: 15AN: 245022Hom.: 0 AF XY: 0.0000529 AC XY: 7AN XY: 132352
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GnomAD4 exome AF: 0.0000172 AC: 25AN: 1451366Hom.: 0 Cov.: 29 AF XY: 0.0000194 AC XY: 14AN XY: 722304
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 151958Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74246
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 17, 2023 | The c.1376C>G (p.S459C) alteration is located in exon 13 (coding exon 12) of the USP33 gene. This alteration results from a C to G substitution at nucleotide position 1376, causing the serine (S) at amino acid position 459 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;.;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
B;B;B;P
Vest4
MutPred
0.38
.;Loss of phosphorylation at S459 (P = 0.0157);Loss of phosphorylation at S459 (P = 0.0157);Loss of phosphorylation at S459 (P = 0.0157);
MVP
MPC
0.047
ClinPred
T
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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