chr1-77697454-A-C
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_201624.3(USP33):āc.2599T>Gā(p.Ser867Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,450,470 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000021 ( 0 hom. )
Consequence
USP33
NM_201624.3 missense
NM_201624.3 missense
Scores
4
5
8
Clinical Significance
Conservation
PhyloP100: 8.80
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USP33 | NM_201624.3 | c.2599T>G | p.Ser867Ala | missense_variant | 24/24 | ENST00000370794.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USP33 | ENST00000370794.7 | c.2599T>G | p.Ser867Ala | missense_variant | 24/24 | 1 | NM_201624.3 | P1 | |
USP33 | ENST00000370793.5 | c.2692T>G | p.Ser898Ala | missense_variant | 25/25 | 1 | |||
USP33 | ENST00000357428.5 | c.2692T>G | p.Ser898Ala | missense_variant | 24/24 | 5 | |||
USP33 | ENST00000481579.5 | c.*33T>G | 3_prime_UTR_variant | 14/14 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.0000126 AC: 3AN: 238716Hom.: 0 AF XY: 0.00000775 AC XY: 1AN XY: 129086
GnomAD3 exomes
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GnomAD4 exome AF: 0.00000207 AC: 3AN: 1450470Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 721326
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ExAC
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1
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 | Dec 28, 2022 | The c.2692T>G (p.S898A) alteration is located in exon 25 (coding exon 24) of the USP33 gene. This alteration results from a T to G substitution at nucleotide position 2692, causing the serine (S) at amino acid position 898 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;.
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
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
0.99
.;D;D
Vest4
MutPred
0.32
.;Loss of disorder (P = 0.0662);Loss of disorder (P = 0.0662);
MVP
MPC
1.5
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at