Variant rs1165222 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.677C>T(p.Thr226Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.852 in 1,612,044 control chromosomes in the GnomAD database, including 585,475 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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 same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.87 ( 57083 hom., cov: 31)

Exomes 𝑓: 0.85 ( 528392 hom. )

Consequence

USP24
NM_015306.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.99

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:

USP24 (HGNC:):

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=5.2791404E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP24	NM_015306.3 linkuse as main transcript	c.677C>T	p.Thr226Ile	missense_variant	4/68	ENST00000294383.7	NP_056121.2	Q9UPU5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP24	ENST00000294383.7 linkuse as main transcript	c.677C>T	p.Thr226Ile	missense_variant	4/68	5	NM_015306.3	ENSP00000294383.5		Q9UPU5
USP24	ENST00000484447.6 linkuse as main transcript	c.677C>T	p.Thr226Ile	missense_variant	4/68	3		ENSP00000489026.2		A0A0U1RQI9

Frequencies

GnomAD3 genomes

AF:

0.865

AC:

131618

AN:

152074

Hom.:

57038

Cov.:

show subpopulations

Gnomad AFR

AF:

0.863

Gnomad AMI

AF:

0.877

Gnomad AMR

AF:

0.900

Gnomad ASJ

AF:

0.819

Gnomad EAS

AF:

0.994

Gnomad SAS

AF:

0.913

Gnomad FIN

AF:

0.876

Gnomad MID

AF:

0.883

Gnomad NFE

AF:

0.846

Gnomad OTH

AF:

0.878

GnomAD3 exomes

AF:

0.877

AC:

217197

AN:

247534

Hom.:

95525

AF XY:

0.875

AC XY:

117424

AN XY:

134256

show subpopulations

Gnomad AFR exome

AF:

0.866

Gnomad AMR exome

AF:

0.929

Gnomad ASJ exome

AF:

0.817

Gnomad EAS exome

AF:

0.996

Gnomad SAS exome

AF:

0.897

Gnomad FIN exome

AF:

0.876

Gnomad NFE exome

AF:

0.844

Gnomad OTH exome

AF:

0.877

GnomAD4 exome

AF:

0.850

AC:

1240968

AN:

1459852

Hom.:

528392

Cov.:

AF XY:

0.851

AC XY:

618115

AN XY:

726166

show subpopulations

Gnomad4 AFR exome

AF:

0.869

Gnomad4 AMR exome

AF:

0.925

Gnomad4 ASJ exome

AF:

0.816

Gnomad4 EAS exome

AF:

0.992

Gnomad4 SAS exome

AF:

0.895

Gnomad4 FIN exome

AF:

0.877

Gnomad4 NFE exome

AF:

0.837

Gnomad4 OTH exome

AF:

0.855

GnomAD4 genome

AF:

0.865

AC:

131721

AN:

152192

Hom.:

57083

Cov.:

AF XY:

0.869

AC XY:

64645

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.863

Gnomad4 AMR

AF:

0.900

Gnomad4 ASJ

AF:

0.819

Gnomad4 EAS

AF:

0.994

Gnomad4 SAS

AF:

0.913

Gnomad4 FIN

AF:

0.876

Gnomad4 NFE

AF:

0.846

Gnomad4 OTH

AF:

0.879

Alfa

AF:

0.848

Hom.:

134755

Bravo

AF:

0.866

TwinsUK

AF:

0.833

AC:

3089

ALSPAC

AF:

0.822

AC:

3168

ESP6500AA

AF:

0.865

AC:

3176

ESP6500EA

AF:

0.844

AC:

6904

ExAC

AF:

0.876

AC:

105749

Asia WGS

AF:

0.951

AC:

3305

AN:

3474

EpiCase

AF:

0.841

EpiControl

AF:

0.837

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.74

DEOGEN2

Benign

0.020

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.12

MetaRNN

Benign

5.3e-7

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.4

PrimateAI

Benign

0.27

PROVEAN

Benign

0.47

REVEL

Benign

0.054

Sift

Benign

0.67

Sift4G

Benign

0.40

Vest4

0.031

MPC

0.48

ClinPred

0.0011

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.025

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over