Variant 4-119248751-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001371395.1(USP53):c.241A>T(p.Ile81Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0121 in 1,611,292 control chromosomes in the GnomAD database, including 166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0090 ( 6 hom., cov: 31)

Exomes 𝑓: 0.012 ( 160 hom. )

Consequence

USP53
NM_001371395.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 6.03

Variant links:

Genes affected

USP53 (HGNC:29255): (ubiquitin specific peptidase 53) Predicted to enable thiol-dependent deubiquitinase. Predicted to be involved in response to auditory stimulus and sensory perception of sound. Predicted to act upstream of or within action potential and neuron apoptotic process. Predicted to be located in bicellular tight junction. Predicted to be active in cell-cell junction. [provided by Alliance of Genome Resources, Apr 2022]

USP53 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=0.014961064).

BP6

Variant 4-119248751-A-T is Benign according to our data. Variant chr4-119248751-A-T is described in ClinVar as [Benign]. Clinvar id is 773456.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00899 (1369/152326) while in subpopulation NFE AF= 0.014 (950/68034). AF 95% confidence interval is 0.0132. There are 6 homozygotes in gnomad4. There are 625 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP53	NM_001371395.1 linkuse as main transcript	c.241A>T	p.Ile81Leu	missense_variant	7/19	ENST00000692078.1	NP_001358324.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP53	ENST00000692078.1 linkuse as main transcript	c.241A>T	p.Ile81Leu	missense_variant	7/19		NM_001371395.1	ENSP00000509606	P2

Frequencies

GnomAD3 genomes

AF:

0.00899

AC:

1369

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00265

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0112

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00424

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0140

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00936

AC:

2307

AN:

246434

Hom.:

AF XY:

0.00985

AC XY:

1316

AN XY:

133550

show subpopulations

Gnomad AFR exome

AF:

0.00233

Gnomad AMR exome

AF:

0.00768

Gnomad ASJ exome

AF:

0.0134

Gnomad EAS exome

AF:

0.0000560

Gnomad SAS exome

AF:

0.00348

Gnomad FIN exome

AF:

0.00460

Gnomad NFE exome

AF:

0.0144

Gnomad OTH exome

AF:

0.0112

GnomAD4 exome

AF:

0.0124

AC:

18056

AN:

1458966

Hom.:

160

Cov.:

AF XY:

0.0121

AC XY:

8810

AN XY:

725624

show subpopulations

Gnomad4 AFR exome

AF:

0.00180

Gnomad4 AMR exome

AF:

0.00794

Gnomad4 ASJ exome

AF:

0.0139

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00392

Gnomad4 FIN exome

AF:

0.00592

Gnomad4 NFE exome

AF:

0.0143

Gnomad4 OTH exome

AF:

0.0121

GnomAD4 genome

AF:

0.00899

AC:

1369

AN:

152326

Hom.:

Cov.:

AF XY:

0.00839

AC XY:

625

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00265

Gnomad4 AMR

AF:

0.0112

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.00424

Gnomad4 NFE

AF:

0.0140

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.0127

Hom.:

Bravo

AF:

0.00935

TwinsUK

AF:

0.0121

AC:

ALSPAC

AF:

0.00986

AC:

ESP6500AA

AF:

0.000784

AC:

ESP6500EA

AF:

0.0137

AC:

113

ExAC

AF:

0.00980

AC:

1185

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	USP53: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.016

T;T

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

.;D

MetaRNN

Benign

0.015

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.11

Sift

Benign

0.18

T;T

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.46

P;P

Vest4

0.47

MutPred

0.62

Gain of ubiquitination at K79 (P = 0.1215);Gain of ubiquitination at K79 (P = 0.1215);

MVP

0.53

MPC

0.16

ClinPred

0.033

GERP RS

6.0

Varity_R

0.085

gMVP

0.50

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