Variant chr5-41925359-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012176.3(FBXO4):c.50T>G(p.Phe17Cys) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

FBXO4
NM_012176.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.243

Variant links:

Genes affected

FBXO4 (HGNC:13583): (F-box protein 4) 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. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

FBXO4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.078650296).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FBXO4	NM_012176.3 linkuse as main transcript	c.50T>G	p.Phe17Cys	missense_variant	1/7	ENST00000281623.8
FBXO4	NM_033484.3 linkuse as main transcript	c.50T>G	p.Phe17Cys	missense_variant	1/5
FBXO4	NM_001297437.2 linkuse as main transcript	c.50T>G	p.Phe17Cys	missense_variant	1/6
FBXO4	XM_011514026.4 linkuse as main transcript	c.50T>G	p.Phe17Cys	missense_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBXO4	ENST00000281623.8 linkuse as main transcript	c.50T>G	p.Phe17Cys	missense_variant	1/7	1	NM_012176.3	P1	Q9UKT5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 24, 2022

The c.50T>G (p.F17C) alteration is located in exon 1 (coding exon 1) of the FBXO4 gene. This alteration results from a T to G substitution at nucleotide position 50, causing the phenylalanine (F) at amino acid position 17 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.64

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.65

T;T;T

M_CAP

Benign

0.040

MetaRNN

Benign

0.079

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.34

N;N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.0

N;N;N

REVEL

Benign

0.15

Sift

Benign

0.13

T;T;T

Sift4G

Benign

0.18

T;T;T

Polyphen

0.22

B;B;B

Vest4

0.19

MutPred

0.17

Gain of catalytic residue at P16 (P = 0.0365);Gain of catalytic residue at P16 (P = 0.0365);Gain of catalytic residue at P16 (P = 0.0365);

MVP

0.48

MPC

0.23

ClinPred

0.073

GERP RS

0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.10

gMVP

0.20

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over