9-129868438-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001110303.4(USP20):c.1124G>T(p.Cys375Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000758 in 1,610,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00035 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000047 ( 0 hom. )
Consequence
USP20
NM_001110303.4 missense
NM_001110303.4 missense
Scores
6
12
Clinical Significance
Conservation
PhyloP100: 3.86
Genes affected
USP20 (HGNC:12619): (ubiquitin specific peptidase 20) This gene encodes a ubiquitin specific processing protease that was first identified as a substrate of the VHL (von Hippel-Lindau disease) protein E3 ubiquitin ligase complex. In addition to being ubiquitinated by the VHL-E3 ligase complex, this enzyme deubiquitinates hypoxia-inducible factor (HIF)-1 alpha and thereby causes increased expression of HIF-1alpha targeted genes which play a role in angiogenesis, glucose metabolism, cell proliferation and metastasis. The enzyme encoded by this gene also regulates G-protein coupled receptor signaling by mediating the deubiquitination of beta-2 adrenergic receptor (ADRB2). This enzyme is a ubiquitously expressed thiolester hydrolase. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jan 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.21823832).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USP20 | NM_001110303.4 | c.1124G>T | p.Cys375Phe | missense_variant | 11/26 | ENST00000372429.8 | |
USP20 | NM_001008563.5 | c.1124G>T | p.Cys375Phe | missense_variant | 11/26 | ||
USP20 | NM_006676.8 | c.1124G>T | p.Cys375Phe | missense_variant | 11/25 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USP20 | ENST00000372429.8 | c.1124G>T | p.Cys375Phe | missense_variant | 11/26 | 1 | NM_001110303.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000342 AC: 52AN: 152168Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000622 AC: 15AN: 241260Hom.: 0 AF XY: 0.0000529 AC XY: 7AN XY: 132206
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GnomAD4 exome AF: 0.0000473 AC: 69AN: 1457944Hom.: 0 Cov.: 84 AF XY: 0.0000262 AC XY: 19AN XY: 724874
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GnomAD4 genome ? AF: 0.000348 AC: 53AN: 152286Hom.: 0 Cov.: 33 AF XY: 0.000349 AC XY: 26AN XY: 74458
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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 | Jun 17, 2022 | The c.1124G>T (p.C375F) alteration is located in exon 11 (coding exon 9) of the USP20 gene. This alteration results from a G to T substitution at nucleotide position 1124, causing the cysteine (C) at amino acid position 375 to be replaced by a phenylalanine (F). 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
Benign
Dann
Benign
DEOGEN2
Benign
T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Benign
T;T;T
Polyphen
P;P;P
Vest4
MVP
MPC
0.47
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