chr1-77714756-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_201624.3(USP33):ā€‹c.2073G>Cā€‹(p.Glu691Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000203 in 1,612,148 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00012 ( 0 hom., cov: 32)
Exomes š‘“: 0.00021 ( 0 hom. )

Consequence

USP33
NM_201624.3 missense

Scores

6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.669
Variant links:
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
USP33NM_201624.3 linkuse as main transcriptc.2073G>C p.Glu691Asp missense_variant 19/24 ENST00000370794.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
USP33ENST00000370794.7 linkuse as main transcriptc.2073G>C p.Glu691Asp missense_variant 19/241 NM_201624.3 P1Q8TEY7-2

Frequencies

GnomAD3 genomes
AF:
0.000125
AC:
19
AN:
152196
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000377
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000718
AC:
18
AN:
250838
Hom.:
0
AF XY:
0.0000664
AC XY:
9
AN XY:
135588
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000277
Gnomad NFE exome
AF:
0.000106
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000212
AC:
309
AN:
1459952
Hom.:
0
Cov.:
31
AF XY:
0.000204
AC XY:
148
AN XY:
726288
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000225
Gnomad4 NFE exome
AF:
0.000261
Gnomad4 OTH exome
AF:
0.0000996
GnomAD4 genome
AF:
0.000125
AC:
19
AN:
152196
Hom.:
0
Cov.:
32
AF XY:
0.000148
AC XY:
11
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000377
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000158
Hom.:
0
Bravo
AF:
0.000102
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.000273
EpiControl
AF:
0.000119

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 submitterclinical testingAmbry GeneticsApr 26, 2023The c.2166G>C (p.E722D) alteration is located in exon 20 (coding exon 19) of the USP33 gene. This alteration results from a G to C substitution at nucleotide position 2166, causing the glutamic acid (E) at amino acid position 722 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.46
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
21
DANN
Uncertain
1.0
Eigen
Benign
-0.23
Eigen_PC
Benign
-0.21
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.94
D;D;.;D
M_CAP
Benign
0.048
D
MetaRNN
Uncertain
0.45
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-1.2
N;N;N;N
REVEL
Benign
0.15
Sift
Benign
0.045
D;T;T;T
Sift4G
Benign
0.58
T;T;T;T
Polyphen
0.98
D;D;D;D
Vest4
0.57
MutPred
0.23
.;Gain of MoRF binding (P = 0.1141);Gain of MoRF binding (P = 0.1141);.;
MVP
0.47
MPC
1.5
ClinPred
0.24
T
GERP RS
2.3
Varity_R
0.12
gMVP
0.65

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs369977044; hg19: chr1-78180441; API