Variant chr15-63504780-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006537.4(USP3):c.41C>A(p.Pro14Gln) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

USP3
NM_006537.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.30

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]

USP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.29853958).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP3	NM_006537.4 link	c.41C>A	p.Pro14Gln	missense_variant	1/15	ENST00000380324.8	NP_006528.2	Q9Y6I4-1
USP3	NM_001256702.2 link	c.41C>A	p.Pro14Gln	missense_variant	1/14		NP_001243631.1	Q9Y6I4-2
USP3	NR_046341.2 link	n.188C>A		non_coding_transcript_exon_variant	1/16
USP3	NR_046342.2 link	n.188C>A		non_coding_transcript_exon_variant	1/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP3	ENST00000380324.8 link	c.41C>A	p.Pro14Gln	missense_variant	1/15	1	NM_006537.4	ENSP00000369681.3		Q9Y6I4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1459154

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725942

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

May 18, 2022

The c.41C>A (p.P14Q) alteration is located in exon 1 (coding exon 1) of the USP3 gene. This alteration results from a C to A substitution at nucleotide position 41, causing the proline (P) at amino acid position 14 to be replaced by a glutamine (Q). 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

0.14

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0041

.;T;T;T

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.044

FATHMM_MKL

Benign

0.67

LIST_S2

Uncertain

0.86

D;D;D;D

M_CAP

Pathogenic

0.99

MetaRNN

Benign

0.30

T;T;T;T

MetaSVM

Uncertain

-0.12

MutationAssessor

Benign

1.5

L;.;.;L

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

1.1

N;N;N;N

REVEL

Uncertain

0.40

Sift

Benign

0.53

T;T;T;T

Sift4G

Benign

0.67

T;T;T;T

Polyphen

0.0020

.;.;.;B

Vest4

0.45

MutPred

0.26

Gain of solvent accessibility (P = 0.0365);Gain of solvent accessibility (P = 0.0365);Gain of solvent accessibility (P = 0.0365);Gain of solvent accessibility (P = 0.0365);

MVP

0.70

MPC

0.44

ClinPred

0.75

GERP RS

4.7

Varity_R

0.12

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over