6-53095546-C-A

Variant names:

• chr6-53095546-C-A
• rs576037107
• NM_033480.3:c.1087C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_033480.3(FBXO9):​c.1087C>A​(p.Arg363Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R363C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FBXO9 NM_033480.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.53
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO9	NM_033480.3	MANE Select	c.1087C>A	p.Arg363Ser	missense	Exon 12 of 13	NP_258441.1	Q9UK97-2
	FBXO9	NM_012347.4		c.1117C>A	p.Arg373Ser	missense	Exon 11 of 12	NP_036479.1	Q9UK97-1
	FBXO9	NM_033481.3		c.985C>A	p.Arg329Ser	missense	Exon 12 of 13	NP_258442.2	Q9UK97-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO9	ENST00000323557.12	TSL:1 MANE Select	c.1087C>A	p.Arg363Ser	missense	Exon 12 of 13	ENSP00000326968.7	Q9UK97-2
	FBXO9	ENST00000244426.10	TSL:1	c.1117C>A	p.Arg373Ser	missense	Exon 11 of 12	ENSP00000244426.6	Q9UK97-1
	FBXO9	ENST00000370939.7	TSL:1	c.985C>A	p.Arg329Ser	missense	Exon 12 of 13	ENSP00000359977.3	Q9UK97-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.091	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Uncertain	-0.085	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		5.5
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.48
Sift	Benign	0.14	T
Sift4G	Benign	0.54	T
Polyphen		0.29	B
Vest4		0.65
MutPred		0.47		Gain of sheet (P = 0.0344)
MVP		0.53
MPC		1.2
ClinPred		0.96	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.49
gMVP		0.55
Mutation Taster		=50/50

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

Other links and lift over

dbSNP: rs576037107; hg19: chr6-52960344; COSMIC: COSV104547349; COSMIC: COSV104547349;