8-123513243-C-T

Position:

• chr8-123513243-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_058229.4(FBXO32):​c.606G>A​(p.Thr202Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,613,960 control chromosomes in the GnomAD database, including 12,624 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1785 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10839 hom.)
• Consequence: FBXO32 NM_058229.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.646

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]

FBXO32 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 8-123513243-C-T is Benign according to our data. Variant chr8-123513243-C-T is described in ClinVar as [Benign]. Clinvar id is 1275067.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.646 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXO32	NM_058229.4	c.606G>A	p.Thr202Thr	synonymous_variant	6/9	ENST00000517956.5	NP_478136.1
FBXO32	NM_148177.3	c.171G>A	p.Thr57Thr	synonymous_variant	3/6		NP_680482.1
FBXO32	NM_001242463.2	c.373-6669G>A		intron_variant			NP_001229392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXO32	ENST00000517956.5	c.606G>A	p.Thr202Thr	synonymous_variant	6/9	1	NM_058229.4	ENSP00000428205.1
FBXO32	ENST00000443022.2	c.373-6669G>A		intron_variant		1		ENSP00000390790.2
FBXO32	ENST00000287396.2	n.480G>A		non_coding_transcript_exon_variant	3/6	1
FBXO32	ENST00000521719.5	n.*31G>A		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20297 AN: 152052 Hom.: 1780 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.0692

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.0860

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0952

Gnomad OTH AF: 0.124

GnomAD3 exomes AF: 0.136 AC: 34176 AN: 251404 Hom.: 3591 AF XY: 0.128 AC XY: 17374 AN XY: 135876

Gnomad AFR exome AF: 0.180

Gnomad AMR exome AF: 0.165

Gnomad ASJ exome AF: 0.0720

Gnomad EAS exome AF: 0.469

Gnomad SAS exome AF: 0.0845

Gnomad FIN exome AF: 0.108

Gnomad NFE exome AF: 0.0933

Gnomad OTH exome AF: 0.110

GnomAD4 exome AF: 0.107 AC: 156539 AN: 1461790 Hom.: 10839 Cov.: 32 AF XY: 0.106 AC XY: 76796 AN XY: 727202

Gnomad4 AFR exome AF: 0.174

Gnomad4 AMR exome AF: 0.157

Gnomad4 ASJ exome AF: 0.0724

Gnomad4 EAS exome AF: 0.415

Gnomad4 SAS exome AF: 0.0828

Gnomad4 FIN exome AF: 0.114

Gnomad4 NFE exome AF: 0.0939

Gnomad4 OTH exome AF: 0.120

GnomAD4 genome AF: 0.134 AC: 20323 AN: 152170 Hom.: 1785 Cov.: 32 AF XY: 0.135 AC XY: 10026 AN XY: 74382

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.0692

Gnomad4 EAS AF: 0.453

Gnomad4 SAS AF: 0.0863

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.0952

Gnomad4 OTH AF: 0.126

Alfa AF: 0.0981 Hom.: 876

Bravo AF: 0.141

Asia WGS AF: 0.247 AC: 857 AN: 3478

EpiCase AF: 0.0924

EpiControl AF: 0.0908

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	3.5
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs3739287; hg19: chr8-124525483; COSMIC: COSV54890522; COSMIC: COSV54890522;