Genetic Variant NM_015306.3:c.7087A>G (chr1-55079651-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_015306.3(USP24):c.7087A>G(p.Ile2363Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000195 in 1,536,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

USP24
NM_015306.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.22

Publications

0 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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0071837306).

BP6

Variant 1-55079651-T-C is Benign according to our data. Variant chr1-55079651-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2616640.Status of the report is criteria_provided_single_submitter, 1 stars.

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.7087A>G	p.Ile2363Val	missense	Exon 60 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.7087A>G	p.Ile2363Val	missense	Exon 60 of 68	ENSP00000294383.5	Q9UPU5
USP24	ENST00000927917.1		c.7084A>G	p.Ile2362Val	missense	Exon 60 of 68	ENSP00000597976.1
USP24	ENST00000484447.6	TSL:3	c.7087A>G	p.Ile2363Val	missense	Exon 60 of 68	ENSP00000489026.2	A0A0U1RQI9

Frequencies

GnomAD3 genomes

AF:

0.0000464

AC:

AN:

150788

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000755

AC:

AN:

185422

AF XY:

0.0000586

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00120

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000166

AC:

AN:

1385810

Hom.:

Cov.:

AF XY:

0.0000131

AC XY:

AN XY:

687634

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28484

American (AMR)

AF:

0.00

AC:

AN:

25516

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23532

East Asian (EAS)

AF:

0.000616

AC:

AN:

35726

South Asian (SAS)

AF:

0.00

AC:

AN:

71886

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52720

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5566

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1085222

Other (OTH)

AF:

0.0000175

AC:

AN:

57158

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

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:

0.0000464

AC:

AN:

150904

Hom.:

Cov.:

AF XY:

0.0000407

AC XY:

AN XY:

73752

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41350

American (AMR)

AF:

0.00

AC:

AN:

15138

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3424

East Asian (EAS)

AF:

0.00135

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4778

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10472

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67280

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.532

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:

0.00

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.000108

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

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

Benign

0.066

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.0010

(source)

DANN

Benign

0.42

DEOGEN2

Benign

0.017

Eigen

Benign

-2.6

Eigen_PC

Benign

-2.6

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.11

M_CAP

Benign

0.0018

MetaRNN

Benign

0.0072

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

PhyloP100

-2.2

PrimateAI

Benign

0.32

PROVEAN

Benign

0.16

REVEL

Benign

0.028

Sift

Benign

0.95

Sift4G

Benign

0.89

Vest4

0.067

MVP

0.082

MPC

0.37

ClinPred

0.0063

GERP RS

-9.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.0098

gMVP

0.080

Mutation Taster

=97/3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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