8-123513243-C-T

Variant names:

• chr8-123513243-C-T
• rs3739287
• NM_058229.4:c.606G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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 Gene-Disease associations (from GenCC):

• dilated cardiomyopathy

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058229.4. 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
	FBXO32	NM_058229.4	MANE Select	c.606G>A	p.Thr202Thr	synonymous	Exon 6 of 9	NP_478136.1	Q969P5-1
	FBXO32	NM_148177.3		c.171G>A	p.Thr57Thr	synonymous	Exon 3 of 6	NP_680482.1	Q0VAQ6
	FBXO32	NM_001242463.2		c.373-6669G>A		intron	N/A	NP_001229392.1	Q969P5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO32	ENST00000517956.5	TSL:1 MANE Select	c.606G>A	p.Thr202Thr	synonymous	Exon 6 of 9	ENSP00000428205.1	Q969P5-1
	FBXO32	ENST00000443022.2	TSL:1	c.373-6669G>A		intron	N/A	ENSP00000390790.2	Q969P5-2
	FBXO32	ENST00000287396.2	TSL:1	n.480G>A		non_coding_transcript_exon	Exon 3 of 6

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

GnomAD2 exomes AF: 0.136 AC: 34176 AN: 251404 AF XY: 0.128

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 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

African (AFR) AF: 0.174 AC: 5822 AN: 33476

American (AMR) AF: 0.157 AC: 6998 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0724 AC: 1891 AN: 26136

East Asian (EAS) AF: 0.415 AC: 16471 AN: 39696

South Asian (SAS) AF: 0.0828 AC: 7146 AN: 86256

European-Finnish (FIN) AF: 0.114 AC: 6076 AN: 53420

Middle Eastern (MID) AF: 0.0852 AC: 491 AN: 5766

European-Non Finnish (NFE) AF: 0.0939 AC: 104388 AN: 1111946

Other (OTH) AF: 0.120 AC: 7256 AN: 60384

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

African (AFR) AF: 0.175 AC: 7259 AN: 41510

American (AMR) AF: 0.137 AC: 2099 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0692 AC: 240 AN: 3470

East Asian (EAS) AF: 0.453 AC: 2340 AN: 5162

South Asian (SAS) AF: 0.0863 AC: 415 AN: 4810

European-Finnish (FIN) AF: 0.106 AC: 1122 AN: 10594

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0952 AC: 6474 AN: 68006

Other (OTH) AF: 0.126 AC: 266 AN: 2114

Alfa AF: 0.0998 Hom.: 1135

Bravo AF: 0.141

Asia WGS AF: 0.247 AC: 857 AN: 3478

EpiCase AF: 0.0924

EpiControl AF: 0.0908

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	3.5
DANN	Benign	0.73
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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