Variant 11-113799350-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001346252.4(USP28):c.3310G>A(p.Val1104Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0016 in 1,614,148 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 2 hom. )

Consequence

USP28
NM_001346252.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.45

Variant links:

Genes affected

USP28 (HGNC:12625): (ubiquitin specific peptidase 28) The protein encoded by this gene is a deubiquitinase involved in the DNA damage pathway and DNA damage-induced apoptosis. Overexpression of this gene is seen in several cancers. [provided by RefSeq, Oct 2016]

USP28 links:

USP28 (HGNC:):

USP28 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009186447).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP28	NM_001346252.4 linkuse as main transcript	c.3310G>A	p.Val1104Ile	missense_variant	26/26	ENST00000696973.1	NP_001333181.1	A0A8V8TLZ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP28	ENST00000696973.1 linkuse as main transcript	c.3310G>A	p.Val1104Ile	missense_variant	26/26		NM_001346252.4	ENSP00000513009.1		A0A8V8TLZ9

Frequencies

GnomAD3 genomes

AF:

0.00106

AC:

162

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00172

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00122

AC:

308

AN:

251454

Hom.:

AF XY:

0.00121

AC XY:

164

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00127

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.00111

Gnomad FIN exome

AF:

0.000416

Gnomad NFE exome

AF:

0.00178

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00165

AC:

2413

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00167

AC XY:

1215

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.00132

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00119

Gnomad4 FIN exome

AF:

0.000431

Gnomad4 NFE exome

AF:

0.00188

Gnomad4 OTH exome

AF:

0.00194

GnomAD4 genome

AF:

0.00106

AC:

162

AN:

152274

Hom.:

Cov.:

AF XY:

0.000953

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00172

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00192

Hom.:

Bravo

AF:

0.00127

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.00129

AC:

157

EpiCase

AF:

0.00300

EpiControl

AF:

0.00202

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

Apr 08, 2022

The c.3124G>A (p.V1042I) alteration is located in exon 25 (coding exon 25) of the USP28 gene. This alteration results from a G to A substitution at nucleotide position 3124, causing the valine (V) at amino acid position 1042 to be replaced by an isoleucine (I). 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

0.074

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.044

T;T;.

Eigen

Benign

0.12

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.78

T;T;T

M_CAP

Benign

0.0062

MetaRNN

Benign

0.0092

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.1

L;.;.

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.63

N;N;N

REVEL

Benign

0.17

Sift

Benign

0.88

T;T;T

Sift4G

Benign

0.85

T;T;T

Polyphen

0.34

B;P;P

Vest4

0.16

MVP

0.28

MPC

0.16

ClinPred

0.023

GERP RS

5.4

Varity_R

0.073

gMVP

0.11

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