Genetic Variant USP24:c.5026-34T>C (chr1-55101737-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015306.3(USP24):c.5026-34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.855 in 1,554,676 control chromosomes in the GnomAD database, including 569,346 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.

Frequency

Genomes: 𝑓 0.87 ( 57052 hom., cov: 30)

Exomes 𝑓: 0.85 ( 512294 hom. )

Consequence

USP24
NM_015306.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.380

Publications

15 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

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.5026-34T>C		intron	N/A	NP_056121.2	Q9UPU5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
USP24	ENST00000294383.7	TSL:5 MANE Select	c.5026-34T>C	intron	N/A	ENSP00000294383.5	Q9UPU5
USP24	ENST00000927917.1		c.5023-34T>C	intron	N/A	ENSP00000597976.1
USP24	ENST00000484447.6	TSL:3	c.5026-34T>C	intron	N/A	ENSP00000489026.2	A0A0U1RQI9

Frequencies

GnomAD3 genomes

AF:

0.865

AC:

131559

AN:

152010

Hom.:

57008

Cov.:

show subpopulations

Gnomad AFR

AF:

0.853

Gnomad AMI

AF:

0.877

Gnomad AMR

AF:

0.900

Gnomad ASJ

AF:

0.825

Gnomad EAS

AF:

0.996

Gnomad SAS

AF:

0.915

Gnomad FIN

AF:

0.879

Gnomad MID

AF:

0.883

Gnomad NFE

AF:

0.851

Gnomad OTH

AF:

0.878

GnomAD2 exomes

AF:

0.881

AC:

162298

AN:

184124

AF XY:

0.880

show subpopulations

Gnomad AFR exome

AF:

0.860

Gnomad AMR exome

AF:

0.928

Gnomad ASJ exome

AF:

0.829

Gnomad EAS exome

AF:

0.997

Gnomad FIN exome

AF:

0.881

Gnomad NFE exome

AF:

0.852

Gnomad OTH exome

AF:

0.884

GnomAD4 exome

AF:

0.854

AC:

1197921

AN:

1402548

Hom.:

512294

Cov.:

AF XY:

0.855

AC XY:

593155

AN XY:

693508

show subpopulations

African (AFR)

AF:

0.861

AC:

26632

AN:

30944

American (AMR)

AF:

0.924

AC:

29895

AN:

32368

Ashkenazi Jewish (ASJ)

AF:

0.823

AC:

19327

AN:

23476

East Asian (EAS)

AF:

0.992

AC:

38134

AN:

38428

South Asian (SAS)

AF:

0.897

AC:

68724

AN:

76646

European-Finnish (FIN)

AF:

0.880

AC:

45052

AN:

51206

Middle Eastern (MID)

AF:

0.899

AC:

4972

AN:

5530

European-Non Finnish (NFE)

AF:

0.843

AC:

915314

AN:

1085866

Other (OTH)

AF:

0.859

AC:

49871

AN:

58084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

7895

15790

23685

31580

39475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20946

41892

62838

83784

104730

<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:

0.865

AC:

131661

AN:

152128

Hom.:

57052

Cov.:

AF XY:

0.869

AC XY:

64603

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.853

AC:

35376

AN:

41488

American (AMR)

AF:

0.901

AC:

13753

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.825

AC:

2864

AN:

3470

East Asian (EAS)

AF:

0.996

AC:

5153

AN:

5176

South Asian (SAS)

AF:

0.914

AC:

4406

AN:

4820

European-Finnish (FIN)

AF:

0.879

AC:

9306

AN:

10584

Middle Eastern (MID)

AF:

0.881

AC:

259

AN:

294

European-Non Finnish (NFE)

AF:

0.851

AC:

57891

AN:

68004

Other (OTH)

AF:

0.879

AC:

1853

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

917

1834

2752

3669

4586

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

894

1788

2682

3576

4470

<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:

0.853

Hom.:

60523

Bravo

AF:

0.866

Asia WGS

AF:

0.950

AC:

3304

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.5

(source)

DANN

Benign

0.33

PhyloP100

0.38

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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