9-129865358-A-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001110303.4(USP20):āc.667A>Gā(p.Met223Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,614,014 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 (ā ).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 33)
Exomes š: 0.000012 ( 0 hom. )
Consequence
USP20
NM_001110303.4 missense
NM_001110303.4 missense
Scores
1
4
13
Clinical Significance
Conservation
PhyloP100: 6.12
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.39289868).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USP20 | NM_001110303.4 | c.667A>G | p.Met223Val | missense_variant | 10/26 | ENST00000372429.8 | |
USP20 | NM_001008563.5 | c.667A>G | p.Met223Val | missense_variant | 10/26 | ||
USP20 | NM_006676.8 | c.667A>G | p.Met223Val | missense_variant | 10/25 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USP20 | ENST00000372429.8 | c.667A>G | p.Met223Val | missense_variant | 10/26 | 1 | NM_001110303.4 | P1 | |
USP20 | ENST00000315480.9 | c.667A>G | p.Met223Val | missense_variant | 10/25 | 1 | P1 | ||
USP20 | ENST00000358355.5 | c.667A>G | p.Met223Val | missense_variant | 10/26 | 1 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152170Hom.: 0 Cov.: 33
GnomAD3 genomes
AF:
AC:
2
AN:
152170
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000401 AC: 10AN: 249570Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135404
GnomAD3 exomes
AF:
AC:
10
AN:
249570
Hom.:
AF XY:
AC XY:
5
AN XY:
135404
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461844Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 727230
GnomAD4 exome
AF:
AC:
18
AN:
1461844
Hom.:
Cov.:
31
AF XY:
AC XY:
11
AN XY:
727230
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152170Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74332
GnomAD4 genome
AF:
AC:
2
AN:
152170
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
74332
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ExAC
AF:
AC:
5
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 | Feb 22, 2023 | The c.667A>G (p.M223V) alteration is located in exon 10 (coding exon 8) of the USP20 gene. This alteration results from a A to G substitution at nucleotide position 667, causing the methionine (M) at amino acid position 223 to be replaced by a valine (V). 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
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
B;B;B
Vest4
MutPred
Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);
MVP
MPC
0.37
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at