chr15-63574385-C-A

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

2
4
12

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

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
USP3NM_006537.4 linkc.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
USP3ENST00000380324.8 linkc.1078C>A p.Pro360Thr missense_variant 11/151 NM_006537.4 ENSP00000369681.3 Q9Y6I4-1

Frequencies

GnomAD3 genomes
AF:
0.0242
AC:
3680
AN:
152070
Hom.:
131
Cov.:
32
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.:
46
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.:
30
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.:
32
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.:
48
Bravo
AF:
0.0280
ESP6500AA
AF:
0.0849
AC:
374
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00776
AC:
942
Asia WGS
AF:
0.00636
AC:
22
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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpSep 19, 2018- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.099
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.21
CADD
Uncertain
25
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
D
LIST_S2
Uncertain
0.97
D;D;D;D;D
MetaRNN
Benign
0.0029
T;T;T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
1.1
.;L;.;.;.
PrimateAI
Uncertain
0.75
T
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
T
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.

Other links and lift over

dbSNP: rs34776764; hg19: chr15-63866584; API