NM_033480.3:c.13G>A

Variant names:

• chr6-53071066-G-A
• rs1768898653
• NM_033480.3:c.13G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033480.3(FBXO9):​c.13G>A​(p.Glu5Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000704 in 1,420,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: FBXO9 NM_033480.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.06
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22998849).

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.13G>A	p.Glu5Lys	missense	Exon 2 of 13	NP_258441.1	Q9UK97-2
	FBXO9	NM_012347.4		c.43G>A	p.Glu15Lys	missense	Exon 1 of 12	NP_036479.1	Q9UK97-1
	FBXO9	NM_033481.3		c.-90G>A		5_prime_UTR	Exon 2 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.13G>A	p.Glu5Lys	missense	Exon 2 of 13	ENSP00000326968.7	Q9UK97-2
	FBXO9	ENST00000244426.10	TSL:1	c.43G>A	p.Glu15Lys	missense	Exon 1 of 12	ENSP00000244426.6	Q9UK97-1
	FBXO9	ENST00000370939.7	TSL:1	c.-90G>A		5_prime_UTR	Exon 2 of 13	ENSP00000359977.3	Q9UK97-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.04e-7 AC: 1 AN: 1420734 Hom.: 0 Cov.: 30 AF XY: 0.00000142 AC XY: 1 AN XY: 702472

African (AFR) AF: 0.00 AC: 0 AN: 32764

American (AMR) AF: 0.00 AC: 0 AN: 38722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25412

East Asian (EAS) AF: 0.00 AC: 0 AN: 38272

South Asian (SAS) AF: 0.00 AC: 0 AN: 80700

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50996

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 9.18e-7 AC: 1 AN: 1089170

Other (OTH) AF: 0.00 AC: 0 AN: 58982

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.17
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.040	T
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.2	L
PhyloP100		7.1
PROVEAN	Benign	-0.70	N
REVEL	Uncertain	0.35
Sift	Benign	0.032	D
Sift4G	Benign	0.61	T
Polyphen		0.37	B
Vest4		0.49
MutPred		0.17		Gain of ubiquitination at E15 (P = 0.0066)
MVP		0.65
MPC		0.51
ClinPred		0.83	D
GERP RS		5.9
PromoterAI		0.0032	Neutral
Varity_R		0.15
gMVP		0.19
Mutation Taster		=276/24	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: rs1768898653; hg19: chr6-52935864;