rs9726

chr22-32491163-C-Gchr22-32491163-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_012179.4(FBXO7):c.949C>G(p.Leu317Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L317L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FBXO7 NM_012179.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.36

Genes affected

FBXO7 (HGNC:13586): (F-box protein 7) 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 it may play a role in regulation of hematopoiesis. Alternatively spliced transcript variants of this gene have been identified with the full-length natures of only some variants being determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.75

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBXO7	NM_012179.4	c.949C>G	p.Leu317Val	missense_variant	6/9	ENST00000266087.12
FBXO7	NM_001033024.2	c.712C>G	p.Leu238Val	missense_variant	6/9
FBXO7	NM_001257990.2	c.607C>G	p.Leu203Val	missense_variant	6/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBXO7	ENST00000266087.12	c.949C>G	p.Leu317Val	missense_variant	6/9	1	NM_012179.4	P2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.078	T;.;.
Eigen	Benign	0.013
Eigen_PC	Benign	0.084
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.023	T
MetaRNN	Pathogenic	0.75	D;D;D
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.7	M;.;.
MutationTaster	Benign	0.034	P;P;P
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.8	N;.;N
REVEL	Benign	0.15
Sift	Uncertain	0.0050	D;.;D
Sift4G	Uncertain	0.019	D;D;D
Polyphen		0.15	B;B;.
Vest4		0.66
MutPred		0.34		Gain of sheet (P = 0.1945);.;.;
MVP		0.44
MPC		0.40
ClinPred		0.92	D
GERP RS		2.4
Varity_R		0.56
gMVP		0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs9726; hg19: chr22-32887150;