Genetic Variant FBXO24:p.Thr536Met (chr7-100600763-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_033506.3(FBXO24):c.1607C>T(p.Thr536Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,613,954 control chromosomes in the GnomAD database, including 42,931 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 5251 hom., cov: 32)

Exomes 𝑓: 0.22 ( 37680 hom. )

Consequence

FBXO24
NM_033506.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.14

Publications

35 publications found

Variant links:

Genes affected

FBXO24 (HGNC:13595): (F-box protein 24) This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of the ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbxs class. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2009]

FBXO24 links:

PCOLCE-AS1 (HGNC:40430): (PCOLCE antisense RNA 1)

PCOLCE-AS1 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 (MetaRNN=0.00285393).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXO24	NM_033506.3 link	c.1607C>T	p.Thr536Met	missense_variant	Exon 10 of 10	ENST00000241071.11	NP_277041.1	O75426-1A4D2D3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXO24	ENST00000241071.11 link	c.1607C>T	p.Thr536Met	missense_variant	Exon 10 of 10	1	NM_033506.3	ENSP00000241071.6		O75426-1

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

38053

AN:

152008

Hom.:

5227

Cov.:

show subpopulations

Gnomad AFR

AF:

0.347

Gnomad AMI

AF:

0.236

Gnomad AMR

AF:

0.178

Gnomad ASJ

AF:

0.242

Gnomad EAS

AF:

0.0183

Gnomad SAS

AF:

0.215

Gnomad FIN

AF:

0.269

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.228

Gnomad OTH

AF:

0.217

GnomAD2 exomes

AF:

0.215

AC:

54109

AN:

251396

AF XY:

0.217

show subpopulations

Gnomad AFR exome

AF:

0.349

Gnomad AMR exome

AF:

0.158

Gnomad ASJ exome

AF:

0.242

Gnomad EAS exome

AF:

0.0152

Gnomad FIN exome

AF:

0.261

Gnomad NFE exome

AF:

0.232

Gnomad OTH exome

AF:

0.216

GnomAD4 exome

AF:

0.222

AC:

324322

AN:

1461828

Hom.:

37680

Cov.:

AF XY:

0.223

AC XY:

161869

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.351

AC:

11763

AN:

33478

American (AMR)

AF:

0.161

AC:

7199

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.238

AC:

6221

AN:

26130

East Asian (EAS)

AF:

0.0122

AC:

483

AN:

39700

South Asian (SAS)

AF:

0.228

AC:

19666

AN:

86258

European-Finnish (FIN)

AF:

0.259

AC:

13814

AN:

53412

Middle Eastern (MID)

AF:

0.190

AC:

1098

AN:

5766

European-Non Finnish (NFE)

AF:

0.225

AC:

250663

AN:

1111970

Other (OTH)

AF:

0.222

AC:

13415

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

16189

32377

48566

64754

80943

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8538

17076

25614

34152

42690

<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:

0.251

AC:

38116

AN:

152126

Hom.:

5251

Cov.:

AF XY:

0.247

AC XY:

18352

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.347

AC:

14398

AN:

41486

American (AMR)

AF:

0.177

AC:

2706

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.242

AC:

840

AN:

3470

East Asian (EAS)

AF:

0.0184

AC:

AN:

5170

South Asian (SAS)

AF:

0.216

AC:

1042

AN:

4826

European-Finnish (FIN)

AF:

0.269

AC:

2846

AN:

10590

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.228

AC:

15477

AN:

67976

Other (OTH)

AF:

0.216

AC:

457

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1460

2920

4379

5839

7299

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

378

756

1134

1512

1890

<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:

0.231

Hom.:

14755

Bravo

AF:

0.249

TwinsUK

AF:

0.222

AC:

825

ALSPAC

AF:

0.220

AC:

847

ESP6500AA

AF:

0.341

AC:

1502

ESP6500EA

AF:

0.233

AC:

2001

ExAC

AF:

0.223

AC:

27120

Asia WGS

AF:

0.117

AC:

409

AN:

3478

EpiCase

AF:

0.221

EpiControl

AF:

0.223

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.0090

T;.;.

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.38

T;T;T

MetaRNN

Benign

0.0029

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-0.81

N;.;.

PhyloP100

3.1

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.77

N;N;N

REVEL

Benign

0.060

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.13

MPC

0.33

ClinPred

0.0060

GERP RS

3.1

Varity_R

0.019

gMVP

0.39

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over