Variant chr15-63574385-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006537.4(USP3):c.1078C>A(p.Pro360Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00442 in 1,603,716 control chromosomes in the GnomAD database, including 271 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.024 ( 131 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 140 hom. )

Consequence

USP3
NM_006537.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.57

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:

USP3-AS1 (HGNC:44140): (USP3 antisense RNA 1)

USP3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028864443).

BP6

Variant 15-63574385-C-A is Benign according to our data. Variant chr15-63574385-C-A is described in ClinVar as [Benign]. Clinvar id is 710052.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP3	NM_006537.4 link	c.1078C>A	p.Pro360Thr	missense_variant	11/15	ENST00000380324.8	NP_006528.2	Q9Y6I4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP3	ENST00000380324.8 link	c.1078C>A	p.Pro360Thr	missense_variant	11/15	1	NM_006537.4	ENSP00000369681.3		Q9Y6I4-1

Frequencies

GnomAD3 genomes

AF:

0.0242

AC:

3680

AN:

152070

Hom.:

131

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0833

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0119

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.0172

GnomAD3 exomes

AF:

0.00581

AC:

1412

AN:

243086

Hom.:

AF XY:

0.00450

AC XY:

592

AN XY:

131536

show subpopulations

Gnomad AFR exome

AF:

0.0805

Gnomad AMR exome

AF:

0.00295

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000140

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000225

Gnomad OTH exome

AF:

0.00340

GnomAD4 exome

AF:

0.00235

AC:

3409

AN:

1451528

Hom.:

140

Cov.:

AF XY:

0.00204

AC XY:

1470

AN XY:

721790

show subpopulations

Gnomad4 AFR exome

AF:

0.0850

Gnomad4 AMR exome

AF:

0.00397

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000251

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000938

Gnomad4 OTH exome

AF:

0.00502

GnomAD4 genome

AF:

0.0242

AC:

3687

AN:

152188

Hom.:

131

Cov.:

AF XY:

0.0235

AC XY:

1749

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0832

Gnomad4 AMR

AF:

0.0118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000177

Gnomad4 OTH

AF:

0.0170

Alfa

AF:

0.00460

Hom.:

Bravo

AF:

0.0280

ESP6500AA

AF:

0.0849

AC:

374

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00776

AC:

942

Asia WGS

AF:

0.00636

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Sep 19, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

.;T;T;T;.

Eigen

Uncertain

0.64

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

D;D;D;D;D

MetaRNN

Benign

0.0029

T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.1

.;L;.;.;.

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-2.0

N;N;N;N;D

REVEL

Benign

0.28

Sift

Benign

0.30

T;T;T;T;T

Sift4G

Benign

0.15

T;T;T;T;T

Polyphen

0.98, 0.97

.;D;D;.;.

Vest4

0.76

MVP

0.21

MPC

1.4

ClinPred

0.027

GERP RS

6.0

Varity_R

0.28

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over