chr8-123506461-GTC-ATT

Variant names:

• chr8-123506461-GTC-ATT
• NM_058229.4:c.763_765delGACinsAAT
• FBXO32 p.Asp255Asn

Variant summary

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

The NM_058229.4(FBXO32):​c.763_765delGACinsAAT​(p.Asp255Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D255H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FBXO32 NM_058229.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.18
• Publications: 0 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: Ambry Genetics, ClinGen

ACMG classification

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

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.763_765delGACinsAAT	p.Asp255Asn	missense	N/A	NP_478136.1	Q969P5-1
	FBXO32	NM_001242463.2		c.484_486delGACinsAAT	p.Asp162Asn	missense	N/A	NP_001229392.1	Q969P5-2
	FBXO32	NM_148177.3		c.328_330delGACinsAAT	p.Asp110Asn	missense	N/A	NP_680482.1	Q0VAQ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO32	ENST00000517956.5	TSL:1 MANE Select	c.763_765delGACinsAAT	p.Asp255Asn	missense	N/A	ENSP00000428205.1	Q969P5-1
	FBXO32	ENST00000443022.2	TSL:1	c.484_486delGACinsAAT	p.Asp162Asn	missense	N/A	ENSP00000390790.2	Q969P5-2
	FBXO32	ENST00000287396.2	TSL:1	n.637_639delGACinsAAT		non_coding_transcript_exon	Exon 4 of 6

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr8-124518701;