6-53095546-C-T

Variant names:

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

Variant summary

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

The NM_033480.3(FBXO9):​c.1087C>T​(p.Arg363Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000223 in 1,612,484 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: FBXO9 NM_033480.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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>T	p.Arg363Cys	missense	Exon 12 of 13	NP_258441.1	Q9UK97-2
	FBXO9	NM_012347.4		c.1117C>T	p.Arg373Cys	missense	Exon 11 of 12	NP_036479.1	Q9UK97-1
	FBXO9	NM_033481.3		c.985C>T	p.Arg329Cys	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>T	p.Arg363Cys	missense	Exon 12 of 13	ENSP00000326968.7	Q9UK97-2
	FBXO9	ENST00000244426.10	TSL:1	c.1117C>T	p.Arg373Cys	missense	Exon 11 of 12	ENSP00000244426.6	Q9UK97-1
	FBXO9	ENST00000370939.7	TSL:1	c.985C>T	p.Arg329Cys	missense	Exon 12 of 13	ENSP00000359977.3	Q9UK97-3

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152134 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000283 AC: 7 AN: 247462 AF XY: 0.0000298

Gnomad AFR exome AF: 0.0000648

Gnomad AMR exome AF: 0.0000295

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000356

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000205 AC: 30 AN: 1460232 Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18 AN XY: 726376

African (AFR) AF: 0.00 AC: 0 AN: 33436

American (AMR) AF: 0.0000451 AC: 2 AN: 44370

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39630

South Asian (SAS) AF: 0.0000349 AC: 3 AN: 85986

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000225 AC: 25 AN: 1111258

Other (OTH) AF: 0.00 AC: 0 AN: 60310

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152252 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74442

African (AFR) AF: 0.0000241 AC: 1 AN: 41544

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.0000282 Hom.: 0

ExAC AF: 0.0000331 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.088	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Uncertain	-0.085	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.5
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.63
Sift	Benign	0.048	D
Sift4G	Uncertain	0.040	D
Polyphen		0.28	B
Vest4		0.59
MutPred		0.55		Gain of sheet (P = 0.0344)
MVP		0.65
MPC		0.64
ClinPred		0.37	T
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.41
gMVP		0.49
Mutation Taster		=60/40	polymorphism

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;