8-123504737-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_058229.4(FBXO32):​c.845G>A​(p.Arg282Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000316 in 1,612,620 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 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

FBXO32
NM_058229.4 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.97
Variant links:
Genes affected
FBXO32 (HGNC:16731): (F-box protein 32) 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 and contains an F-box domain. This protein is highly expressed during muscle atrophy, whereas mice deficient in this gene were found to be resistant to atrophy. This protein is thus a potential drug target for the treatment of muscle atrophy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.13442913).
BS2
High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FBXO32NM_058229.4 linkc.845G>A p.Arg282Gln missense_variant Exon 8 of 9 ENST00000517956.5 NP_478136.1 Q969P5-1A0A024R9F3
FBXO32NM_001242463.2 linkc.566G>A p.Arg189Gln missense_variant Exon 6 of 7 NP_001229392.1 Q969P5-2
FBXO32NM_148177.3 linkc.410G>A p.Arg137Gln missense_variant Exon 5 of 6 NP_680482.1 Q0VAQ6Q498Y9I6L984

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FBXO32ENST00000517956.5 linkc.845G>A p.Arg282Gln missense_variant Exon 8 of 9 1 NM_058229.4 ENSP00000428205.1 Q969P5-1
FBXO32ENST00000443022.2 linkc.566G>A p.Arg189Gln missense_variant Exon 6 of 7 1 ENSP00000390790.2 Q969P5-2
FBXO32ENST00000287396.2 linkn.719G>A non_coding_transcript_exon_variant Exon 5 of 6 1
FBXO32ENST00000524000.5 linkn.245G>A non_coding_transcript_exon_variant Exon 2 of 3 2

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152124
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000189
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000761
AC:
19
AN:
249642
Hom.:
0
AF XY:
0.0000741
AC XY:
10
AN XY:
134954
show subpopulations
Gnomad AFR exome
AF:
0.000247
Gnomad AMR exome
AF:
0.0000882
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000663
Gnomad FIN exome
AF:
0.000231
Gnomad NFE exome
AF:
0.0000442
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000308
AC:
45
AN:
1460378
Hom.:
0
Cov.:
30
AF XY:
0.0000289
AC XY:
21
AN XY:
726462
show subpopulations
Gnomad4 AFR exome
AF:
0.0000898
Gnomad4 AMR exome
AF:
0.0000676
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000582
Gnomad4 FIN exome
AF:
0.000169
Gnomad4 NFE exome
AF:
0.0000162
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152242
Hom.:
0
Cov.:
32
AF XY:
0.0000672
AC XY:
5
AN XY:
74428
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000189
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000453
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000824
AC:
10
EpiCase
AF:
0.000109
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 14, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.845G>A (p.R282Q) alteration is located in exon 8 (coding exon 8) of the FBXO32 gene. This alteration results from a G to A substitution at nucleotide position 845, causing the arginine (R) at amino acid position 282 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.51
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.15
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.21
T;.
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.96
D;D
M_CAP
Benign
0.0081
T
MetaRNN
Benign
0.13
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.8
L;.
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
0.030
N;N
REVEL
Benign
0.15
Sift
Benign
0.16
T;T
Sift4G
Benign
0.21
T;T
Polyphen
0.98
D;.
Vest4
0.43
MVP
0.58
MPC
0.75
ClinPred
0.12
T
GERP RS
5.2
Varity_R
0.22
gMVP
0.57

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs372778187; hg19: chr8-124516977; API