Variant rs487230 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015306.3(USP24):c.7403T>C(p.Val2468Ala) variant causes a missense change. The variant allele was found at a frequency of 0.75 in 1,599,694 control chromosomes in the GnomAD database, including 458,963 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.65 ( 35917 hom., cov: 31)

Exomes 𝑓: 0.76 ( 423046 hom. )

Consequence

USP24
NM_015306.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.12

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.791758E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP24	NM_015306.3 link	c.7403T>C	p.Val2468Ala	missense_variant	63/68	ENST00000294383.7	NP_056121.2	Q9UPU5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP24	ENST00000294383.7 link	c.7403T>C	p.Val2468Ala	missense_variant	63/68	5	NM_015306.3	ENSP00000294383.5		Q9UPU5
USP24	ENST00000484447.6 link	c.7403T>C	p.Val2468Ala	missense_variant	63/68	3		ENSP00000489026.2		A0A0U1RQI9

Frequencies

GnomAD3 genomes

AF:

0.655

AC:

99565

AN:

151926

Hom.:

35908

Cov.:

show subpopulations

Gnomad AFR

AF:

0.327

Gnomad AMI

AF:

0.768

Gnomad AMR

AF:

0.813

Gnomad ASJ

AF:

0.728

Gnomad EAS

AF:

0.906

Gnomad SAS

AF:

0.845

Gnomad FIN

AF:

0.769

Gnomad MID

AF:

0.816

Gnomad NFE

AF:

0.761

Gnomad OTH

AF:

0.720

GnomAD3 exomes

AF:

0.767

AC:

176798

AN:

230382

Hom.:

69772

AF XY:

0.772

AC XY:

96011

AN XY:

124364

show subpopulations

Gnomad AFR exome

AF:

0.309

Gnomad AMR exome

AF:

0.876

Gnomad ASJ exome

AF:

0.724

Gnomad EAS exome

AF:

0.907

Gnomad SAS exome

AF:

0.825

Gnomad FIN exome

AF:

0.770

Gnomad NFE exome

AF:

0.761

Gnomad OTH exome

AF:

0.790

GnomAD4 exome

AF:

0.760

AC:

1100278

AN:

1447650

Hom.:

423046

Cov.:

AF XY:

0.763

AC XY:

548582

AN XY:

718902

show subpopulations

Gnomad4 AFR exome

AF:

0.309

Gnomad4 AMR exome

AF:

0.868

Gnomad4 ASJ exome

AF:

0.726

Gnomad4 EAS exome

AF:

0.901

Gnomad4 SAS exome

AF:

0.827

Gnomad4 FIN exome

AF:

0.774

Gnomad4 NFE exome

AF:

0.760

Gnomad4 OTH exome

AF:

0.748

GnomAD4 genome

AF:

0.655

AC:

99588

AN:

152044

Hom.:

35917

Cov.:

AF XY:

0.663

AC XY:

49313

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.326

Gnomad4 AMR

AF:

0.814

Gnomad4 ASJ

AF:

0.728

Gnomad4 EAS

AF:

0.907

Gnomad4 SAS

AF:

0.844

Gnomad4 FIN

AF:

0.769

Gnomad4 NFE

AF:

0.761

Gnomad4 OTH

AF:

0.723

Alfa

AF:

0.748

Hom.:

111329

Bravo

AF:

0.644

TwinsUK

AF:

0.763

AC:

2829

ALSPAC

AF:

0.750

AC:

2892

ESP6500AA

AF:

0.357

AC:

1310

ESP6500EA

AF:

0.767

AC:

6284

ExAC

AF:

0.750

AC:

90306

Asia WGS

AF:

0.840

AC:

2922

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.023

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.18

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.79

MetaRNN

Benign

7.8e-7

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.49

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.40

REVEL

Benign

0.078

Sift

Benign

0.37

Sift4G

Benign

0.35

Vest4

0.15

MPC

0.53

ClinPred

0.015

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.023

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over