chr1-77697404-T-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_201624.3(USP33):c.2649A>T(p.Glu883Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,613,358 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 0.00017 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000013 ( 0 hom. )
Consequence
USP33
NM_201624.3 missense
NM_201624.3 missense
Scores
10
7
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.777
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]
Genome browser will be placed here
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=0.17412862).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USP33 | NM_201624.3 | c.2649A>T | p.Glu883Asp | missense_variant | 24/24 | ENST00000370794.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USP33 | ENST00000370794.7 | c.2649A>T | p.Glu883Asp | missense_variant | 24/24 | 1 | NM_201624.3 | P1 | |
USP33 | ENST00000370793.5 | c.2742A>T | p.Glu914Asp | missense_variant | 25/25 | 1 | |||
USP33 | ENST00000357428.5 | c.2742A>T | p.Glu914Asp | missense_variant | 24/24 | 5 | |||
USP33 | ENST00000481579.5 | c.*83A>T | 3_prime_UTR_variant | 14/14 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000171 AC: 26AN: 152086Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
26
AN:
152086
Hom.:
Cov.:
32
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: 0.0000239 AC: 6AN: 250642Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135434
GnomAD3 exomes
AF:
AC:
6
AN:
250642
Hom.:
AF XY:
AC XY:
2
AN XY:
135434
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: 0.0000130 AC: 19AN: 1461272Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 726932
GnomAD4 exome
AF:
AC:
19
AN:
1461272
Hom.:
Cov.:
31
AF XY:
AC XY:
5
AN XY:
726932
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: 0.000171 AC: 26AN: 152086Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74266
GnomAD4 genome
AF:
AC:
26
AN:
152086
Hom.:
Cov.:
32
AF XY:
AC XY:
13
AN XY:
74266
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
5
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
1.0
.;D;D
Vest4
MutPred
0.45
.;Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP
MPC
1.4
ClinPred
D
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