Genetic Variant FBXO9:p.Glu26Ala (chr6-53071130-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033480.3(FBXO9):c.77A>C(p.Glu26Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000448 in 1,560,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

FBXO9
NM_033480.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.88

Publications

0 publications found

Variant links:

Genes affected

FBXO9 (HGNC:13588): (F-box protein 9) 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. Alternative splicing of this gene generates at least 3 transcript variants diverging at the 5' terminus. [provided by RefSeq, Jul 2008]

FBXO9 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19548264).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033480.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FBXO9	NM_033480.3	MANE Select	c.77A>C	p.Glu26Ala	missense	Exon 2 of 13	NP_258441.1	Q9UK97-2
FBXO9	NM_012347.4		c.107A>C	p.Glu36Ala	missense	Exon 1 of 12	NP_036479.1	Q9UK97-1
FBXO9	NM_033481.3		c.-26A>C		5_prime_UTR	Exon 2 of 13	NP_258442.2	Q9UK97-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FBXO9	ENST00000323557.12	TSL:1 MANE Select	c.77A>C	p.Glu26Ala	missense	Exon 2 of 13	ENSP00000326968.7	Q9UK97-2
FBXO9	ENST00000244426.10	TSL:1	c.107A>C	p.Glu36Ala	missense	Exon 1 of 12	ENSP00000244426.6	Q9UK97-1
FBXO9	ENST00000370939.7	TSL:1	c.-26A>C		5_prime_UTR	Exon 2 of 13	ENSP00000359977.3	Q9UK97-3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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:

0.00000589

AC:

AN:

169676

AF XY:

0.0000111

show subpopulations

Gnomad AFR exome

AF:

0.000104

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000213

AC:

AN:

1408780

Hom.:

Cov.:

AF XY:

0.00000288

AC XY:

AN XY:

695528

show subpopulations

African (AFR)

AF:

0.0000619

AC:

AN:

32292

American (AMR)

AF:

0.0000271

AC:

AN:

36880

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25286

East Asian (EAS)

AF:

0.00

AC:

AN:

37210

South Asian (SAS)

AF:

0.00

AC:

AN:

79882

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50180

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1082888

Other (OTH)

AF:

0.00

AC:

AN:

58460

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.0000263

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41452

American (AMR)

AF:

0.0000654

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

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:

0.0000329

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.00000866

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

Benign

0.13

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.072

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.77

M_CAP

Benign

0.054

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.65

MutationAssessor

Benign

1.8

PhyloP100

3.9

PROVEAN

Benign

-2.0

REVEL

Uncertain

0.29

Sift

Benign

0.086

Sift4G

Benign

0.44

Polyphen

0.28

Vest4

0.33

MutPred

0.22

Gain of helix (P = 0.0325)

MVP

0.53

MPC

0.66

ClinPred

0.24

GERP RS

5.9

PromoterAI

0.0086

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.17

Mutation Taster

=55/45

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