22-32491163-CTG-GTT

Variant names:

• chr22-32491163-CTG-GTT
• NM_012179.4:c.949_951delCTGinsGTT
• FBXO7 p.Leu317Val

Variant summary

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

The NM_012179.4(FBXO7):​c.949_951delCTGinsGTT​(p.Leu317Val) variant causes a missense change. 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. 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: 6.10
• Publications: 0 publications found

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]

FBXO7 Gene-Disease associations (from GenCC):

• parkinsonian-pyramidal syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012179.4. 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
	FBXO7	NM_012179.4	MANE Select	c.949_951delCTGinsGTT	p.Leu317Val	missense	N/A	NP_036311.3
	FBXO7	NM_001033024.2		c.712_714delCTGinsGTT	p.Leu238Val	missense	N/A	NP_001028196.1	Q9Y3I1-2
	FBXO7	NM_001257990.2		c.607_609delCTGinsGTT	p.Leu203Val	missense	N/A	NP_001244919.1	Q9Y3I1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO7	ENST00000266087.12	TSL:1 MANE Select	c.949_951delCTGinsGTT	p.Leu317Val	missense	N/A	ENSP00000266087.7	Q9Y3I1-1
	FBXO7	ENST00000886524.1		c.949_951delCTGinsGTT	p.Leu317Val	missense	N/A	ENSP00000556583.1
	FBXO7	ENST00000920428.1		c.949_951delCTGinsGTT	p.Leu317Val	missense	N/A	ENSP00000590487.1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.1

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: chr22-32887150;