dbSNP rs9726: FBXO7:p.Leu317Val (chr22-32491163-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.36

Publications

31 publications found

Variant links:

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

FBXO7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.75

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FBXO7	NM_012179.4	MANE Select	c.949C>G	p.Leu317Val	missense	Exon 6 of 9	NP_036311.3
FBXO7	NM_001033024.2		c.712C>G	p.Leu238Val	missense	Exon 6 of 9	NP_001028196.1	Q9Y3I1-2
FBXO7	NM_001257990.2		c.607C>G	p.Leu203Val	missense	Exon 6 of 9	NP_001244919.1	Q9Y3I1-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FBXO7	ENST00000266087.12	TSL:1 MANE Select	c.949C>G	p.Leu317Val	missense	Exon 6 of 9	ENSP00000266087.7	Q9Y3I1-1
FBXO7	ENST00000886524.1		c.949C>G	p.Leu317Val	missense	Exon 6 of 10	ENSP00000556583.1
FBXO7	ENST00000920428.1		c.949C>G	p.Leu317Val	missense	Exon 6 of 9	ENSP00000590487.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.078

Eigen

Benign

0.013

Eigen_PC

Benign

0.084

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.023

MetaRNN

Pathogenic

0.75

MetaSVM

Benign

-0.79

MutationAssessor

Uncertain

2.7

PhyloP100

2.4

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.8

REVEL

Benign

0.15

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.019

Polyphen

0.15

Vest4

0.66

MutPred

0.34

Gain of sheet (P = 0.1945)

MVP

0.44

MPC

0.40

ClinPred

0.92

GERP RS

2.4

Varity_R

0.56

gMVP

0.44

Mutation Taster

=64/36

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over