Genetic Variant USP24:p.Met2485Ile (chr1-55073899-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_015306.3(USP24):c.7455G>A(p.Met2485Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000553 in 1,573,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

USP24
NM_015306.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.16

Publications

2 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20855582).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015306.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP24	NM_015306.3	MANE Select	c.7455G>A	p.Met2485Ile	missense	Exon 64 of 68	NP_056121.2	Q9UPU5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
USP24	ENST00000294383.7	TSL:5 MANE Select	c.7455G>A	p.Met2485Ile	missense	Exon 64 of 68	ENSP00000294383.5	Q9UPU5
USP24	ENST00000927917.1		c.7452G>A	p.Met2484Ile	missense	Exon 64 of 68	ENSP00000597976.1
USP24	ENST00000484447.6	TSL:3	c.7455G>A	p.Met2485Ile	missense	Exon 64 of 68	ENSP00000489026.2	A0A0U1RQI9

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.0000585

AC:

AN:

187972

AF XY:

0.0000704

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000336

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000100

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000528

AC:

AN:

1421114

Hom.:

Cov.:

AF XY:

0.0000541

AC XY:

AN XY:

702578

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32586

American (AMR)

AF:

0.00

AC:

AN:

38560

Ashkenazi Jewish (ASJ)

AF:

0.000433

AC:

AN:

25386

East Asian (EAS)

AF:

0.00

AC:

AN:

37896

South Asian (SAS)

AF:

0.00

AC:

AN:

80458

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50990

Middle Eastern (MID)

AF:

0.000523

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.0000495

AC:

AN:

1090464

Other (OTH)

AF:

0.000119

AC:

AN:

59040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41524

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68008

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000180

Hom.:

Bravo

AF:

0.000136

ExAC

AF:

0.0000336

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Uncertain

0.018

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.021

Eigen

Benign

0.12

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.048

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.80

MutationAssessor

Benign

-0.045

PhyloP100

7.2

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

0.21

REVEL

Uncertain

0.36

Sift

Benign

1.0

Sift4G

Uncertain

0.027

Vest4

0.68

MVP

0.47

MPC

0.50

ClinPred

0.18

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.22

gMVP

0.40

Mutation Taster

=64/36

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over