FBXO7 p.Met115Ile

Variant names:

• chr22-32479203-G-T
• NM_012179.4:c.345G>T
• FBXO7 p.Met115Ile

Your query was ambiguous. Multiple possible variants found:

• chr22-32479203-G-T
• chr22-32479203-G-C
• chr22-32479203-G-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012179.4(FBXO7):​c.345G>T​(p.Met115Ile) 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 benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: FBXO7 NM_012179.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037662625).

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.345G>T	p.Met115Ile	missense	Exon 2 of 9	NP_036311.3
	FBXO7	NM_001257990.2		c.3G>T	p.Met1?	start_lost	Exon 2 of 9	NP_001244919.1	Q9Y3I1-3
	FBXO7	NM_001033024.2		c.108G>T	p.Met36Ile	missense	Exon 2 of 9	NP_001028196.1	Q9Y3I1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO7	ENST00000266087.12	TSL:1 MANE Select	c.345G>T	p.Met115Ile	missense	Exon 2 of 9	ENSP00000266087.7	Q9Y3I1-1
	FBXO7	ENST00000397426.5	TSL:2	c.3G>T	p.Met1?	start_lost	Exon 2 of 9	ENSP00000380571.1	Q9Y3I1-3
	FBXO7	ENST00000444207.1	TSL:2	c.3G>T	p.Met1?	start_lost	Exon 2 of 3	ENSP00000404388.1	A2A282

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 49

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	2.0
DANN	Benign	0.38
DEOGEN2	Benign	0.033	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.082	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.0	N
PhyloP100		-0.027
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.089
Sift	Benign	0.22	T
Sift4G	Benign	0.32	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.031
gMVP		0.078
Mutation Taster		=120/80	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr22-32875190;