Variant 1-55079557-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2

The NM_015306.3(USP24):c.7181G>C(p.Gly2394Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000196 in 1,575,028 control chromosomes in the GnomAD database, including 10 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 0.00035 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 8 hom. )

Consequence

USP24
NM_015306.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.15

Variant links:

Genes affected

USP24 (HGNC:12623): (ubiquitin specific peptidase 24) Modification of cellular proteins by ubiquitin is an essential regulatory mechanism controlled by the coordinated action of multiple ubiquitin-conjugating and deubiquitinating enzymes. USP24 belongs to a large family of cysteine proteases that function as deubiquitinating enzymes (Quesada et al., 2004 [PubMed 14715245]).[supplied by OMIM, Mar 2008]

USP24 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PP2

Missense variant where missense usually causes diseases, USP24

BP4

Computational evidence support a benign effect (MetaRNN=0.009641975).

BS2

High Homozygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP24	NM_015306.3 linkuse as main transcript	c.7181G>C	p.Gly2394Ala	missense_variant	60/68	ENST00000294383.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP24	ENST00000294383.7 linkuse as main transcript	c.7181G>C	p.Gly2394Ala	missense_variant	60/68	5	NM_015306.3	P1
USP24	ENST00000484447.6 linkuse as main transcript	c.7181G>C	p.Gly2394Ala	missense_variant	60/68	3

Frequencies

GnomAD3 genomes

AF:

0.000355

AC:

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00308

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000261

AC:

AN:

214330

Hom.:

AF XY:

0.000248

AC XY:

AN XY:

116886

show subpopulations

Gnomad AFR exome

AF:

0.000366

Gnomad AMR exome

AF:

0.0000808

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00296

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000976

Gnomad OTH exome

AF:

0.00101

GnomAD4 exome

AF:

0.000179

AC:

255

AN:

1422812

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

133

AN XY:

706224

show subpopulations

Gnomad4 AFR exome

AF:

0.000161

Gnomad4 AMR exome

AF:

0.0000849

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00269

Gnomad4 SAS exome

AF:

0.0000130

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000637

Gnomad4 OTH exome

AF:

0.00235

GnomAD4 genome

AF:

0.000355

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00309

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000217

Hom.:

Bravo

AF:

0.000325

ESP6500AA

AF:

0.000267

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000331

AC:

Asia WGS

AF:

0.00664

AC:

AN:

3478

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

Sep 26, 2023

The c.7181G>C (p.G2394A) alteration is located in exon 60 (coding exon 60) of the USP24 gene. This alteration results from a G to C substitution at nucleotide position 7181, causing the glycine (G) at amino acid position 2394 to be replaced by an alanine (A). 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

0.21

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.30

Cadd

Benign

Dann

Benign

0.95

DEOGEN2

Benign

0.049

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.033

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.014

MetaRNN

Benign

0.0096

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.63

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-2.0

REVEL

Benign

0.17

Sift

Benign

0.59

Sift4G

Benign

0.42

Vest4

0.54

MVP

0.22

MPC

0.48

ClinPred

0.030

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.38

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