15-63553792-T-G

Position:

• chr15-63553792-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006537.4(USP3):​c.362T>G​(p.Leu121Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: USP3 NM_006537.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.01

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]

USP3 (HGNC:):

ACMG classification

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=0.4041066).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP3	NM_006537.4	c.362T>G	p.Leu121Trp	missense_variant	4/15	ENST00000380324.8	NP_006528.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP3	ENST00000380324.8	c.362T>G	p.Leu121Trp	missense_variant	4/15	1	NM_006537.4	ENSP00000369681.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 20, 2024

The c.362T>G (p.L121W) alteration is located in exon 4 (coding exon 4) of the USP3 gene. This alteration results from a T to G substitution at nucleotide position 362, causing the leucine (L) at amino acid position 121 to be replaced by a tryptophan (W). 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	0.43
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	26
DANN	Benign	0.96
DEOGEN2	Benign	0.092	.;T;T;T;T;T;.
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;D;D
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.40	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	.;.;L;.;.;.;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.2	N;N;N;D;N;N;N
REVEL	Benign	0.22
Sift	Benign	0.033	D;D;D;D;D;D;D
Sift4G	Benign	0.14	T;T;T;D;T;T;D
Polyphen		0.012, 0.0050	.;.;B;.;B;.;.
Vest4		0.59
MutPred		0.33		.;.;Loss of stability (P = 0.0316);.;.;.;.;
MVP		0.41
MPC		1.5
ClinPred		0.78	D
GERP RS		5.9
Varity_R		0.21

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: chr15-63845991;