5-15928132-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_012304.5(FBXL7):​c.370C>G​(p.Gln124Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 152,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Consequence

FBXL7
NM_012304.5 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.87
Variant links:
Genes affected
FBXL7 (HGNC:13604): (F-box and leucine rich repeat protein 7) This gene encodes a member of the F-box protein family which is characterized by a 42-48 amino acid motif, the F-box, which binds to the S-phase kinase-associated protein 1 (Skp1) protein. The F-box proteins constitute one of the four subunits of E3 ubiquitin protein ligases called SCFs (SKP1-Cul1-F-box), which play a role in phosphorylation-dependent ubiquitination of proteins. The F-box proteins are divided into 3 subfamilies based on the other domain in the protein: F-box proteins that also have a WD-40 domain (Fbws subfamily), F-box proteins that also have leucine-rich repeats (Fbls subfamily) and F-box proteins that contain other motifs or lack known protein-interaction domains (Fbxs subfamily). The protein encoded by this gene belongs to the Fbls subfamily. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, May 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.35066795).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FBXL7NM_012304.5 linkc.370C>G p.Gln124Glu missense_variant Exon 3 of 4 ENST00000504595.2 NP_036436.1 Q9UJT9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FBXL7ENST00000504595.2 linkc.370C>G p.Gln124Glu missense_variant Exon 3 of 4 1 NM_012304.5 ENSP00000423630.1 Q9UJT9-1
FBXL7ENST00000510662.1 linkc.229C>G p.Gln77Glu missense_variant Exon 3 of 4 1 ENSP00000425184.1 Q9UJT9-2
FBXL7ENST00000329673.8 linkc.244C>G p.Gln82Glu missense_variant Exon 1 of 2 2 ENSP00000329632.8 J3KNM9

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152042
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
36
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
152042
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74244
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 24, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.370C>G (p.Q124E) alteration is located in exon 3 (coding exon 3) of the FBXL7 gene. This alteration results from a C to G substitution at nucleotide position 370, causing the glutamine (Q) at amino acid position 124 to be replaced by a glutamic acid (E). 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
0.10
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.030
T;.;.
Eigen
Benign
0.049
Eigen_PC
Uncertain
0.23
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.89
D;D;D
M_CAP
Benign
0.0097
T
MetaRNN
Benign
0.35
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.020
N;.;.
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-0.67
N;N;.
REVEL
Benign
0.10
Sift
Benign
0.031
D;D;.
Sift4G
Uncertain
0.059
T;T;T
Polyphen
0.18
B;.;.
Vest4
0.48
MutPred
0.58
Gain of helix (P = 0.0854);.;.;
MVP
0.63
MPC
0.82
ClinPred
0.55
D
GERP RS
5.7
Varity_R
0.14
gMVP
0.51

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1405117666; hg19: chr5-15928241; API