15-63537078-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006537.4(USP3):​c.206C>G​(p.Thr69Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

USP3
NM_006537.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.255
Variant links:
Genes affected
USP3 (HGNC:12626): (ubiquitin specific peptidase 3) Enables histone binding activity and thiol-dependent deubiquitinase. Involved in several processes, including DNA repair; histone deubiquitination; and regulation of protein stability. Located in several cellular components, including Flemming body; cytoplasmic ribonucleoprotein granule; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.066649884).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
USP3NM_006537.4 linkc.206C>G p.Thr69Ser missense_variant Exon 3 of 15 ENST00000380324.8 NP_006528.2 Q9Y6I4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
USP3ENST00000380324.8 linkc.206C>G p.Thr69Ser missense_variant Exon 3 of 15 1 NM_006537.4 ENSP00000369681.3 Q9Y6I4-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 10, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.206C>G (p.T69S) alteration is located in exon 3 (coding exon 3) of the USP3 gene. This alteration results from a C to G substitution at nucleotide position 206, causing the threonine (T) at amino acid position 69 to be replaced by a serine (S). 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
Benign
0.060
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
13
DANN
Benign
0.92
DEOGEN2
Benign
0.0062
T;T;T;T;T
Eigen
Benign
-0.70
Eigen_PC
Benign
-0.48
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Benign
0.56
T;T;T;T;T
M_CAP
Benign
0.0046
T
MetaRNN
Benign
0.067
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.47
.;N;.;.;.
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-0.51
N;N;N;N;N
REVEL
Benign
0.092
Sift
Benign
0.53
T;T;T;T;T
Sift4G
Benign
0.30
T;T;T;T;T
Polyphen
0.0
.;B;.;B;.
Vest4
0.23, 0.17, 0.19
MutPred
0.47
.;Gain of ubiquitination at K72 (P = 0.0571);.;.;.;
MVP
0.36
MPC
0.42
ClinPred
0.057
T
GERP RS
1.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.052

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-63829277; API