Genetic Variant FBXL5:p.Val324Leu (chr4-15627956-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012161.4(FBXL5):c.970G>C(p.Val324Leu) 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. V324I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

FBXL5
NM_012161.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.46

Publications

0 publications found

Variant links:

Genes affected

FBXL5 (HGNC:13602): (F-box and leucine rich repeat protein 5) 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 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 Fbls class and, in addition to an F-box, contains several tandem leucine-rich repeats. Alternatively spliced transcript variants have been described for this locus. [provided by RefSeq, Aug 2010]

FBXL5 links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.089187086).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012161.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FBXL5	NM_012161.4	MANE Select	c.970G>C	p.Val324Leu	missense	Exon 7 of 11	NP_036293.1	Q9UKA1-1
FBXL5	NM_001193534.2		c.967G>C	p.Val323Leu	missense	Exon 7 of 11	NP_001180463.1
FBXL5	NM_001193535.2		c.919G>C	p.Val307Leu	missense	Exon 7 of 11	NP_001180464.1	Q9UKA1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FBXL5	ENST00000341285.8	TSL:1 MANE Select	c.970G>C	p.Val324Leu	missense	Exon 7 of 11	ENSP00000344866.3	Q9UKA1-1
FBXL5	ENST00000412094.6	TSL:1	c.919G>C	p.Val307Leu	missense	Exon 7 of 11	ENSP00000408679.2	Q9UKA1-2
FBXL5	ENST00000513163.5	TSL:1	c.730G>C	p.Val244Leu	missense	Exon 5 of 9	ENSP00000425472.1	H0Y9Y0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

8.5

(source)

DANN

Benign

0.52

DEOGEN2

Benign

0.057

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.0066

MetaRNN

Benign

0.089

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.27

PhyloP100

1.5

PrimateAI

Benign

0.39

PROVEAN

Benign

0.57

REVEL

Benign

0.028

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.010

Vest4

0.19

MutPred

0.33

Gain of catalytic residue at V324 (P = 0.0149)

MVP

0.26

MPC

0.13

ClinPred

0.13

GERP RS

0.98

Varity_R

0.14

gMVP

0.34

Mutation Taster

=96/4

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