19-45712052-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001080469.2(FBXO46):​c.1444G>A​(p.Val482Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

FBXO46
NM_001080469.2 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.04
Variant links:
Genes affected
FBXO46 (HGNC:25069): (F-box protein 46) Members of the F-box protein family, such as FBXO46, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (MIM 601434), cullin (see CUL1; MIM 603134), and F-box proteins, act as protein-ubiquitin ligases. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains (Jin et al., 2004 [PubMed 15520277]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FBXO46NM_001080469.2 linkc.1444G>A p.Val482Ile missense_variant Exon 2 of 2 ENST00000317683.4 NP_001073938.1 Q6PJ61

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FBXO46ENST00000317683.4 linkc.1444G>A p.Val482Ile missense_variant Exon 2 of 2 2 NM_001080469.2 ENSP00000410007.1 Q6PJ61

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
36
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 21, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1444G>A (p.V482I) alteration is located in exon 2 (coding exon 1) of the FBXO46 gene. This alteration results from a G to A substitution at nucleotide position 1444, causing the valine (V) at amino acid position 482 to be replaced by an isoleucine (I). 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
0.22
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.20
T
Eigen
Uncertain
0.27
Eigen_PC
Uncertain
0.24
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.79
T
M_CAP
Benign
0.013
T
MetaRNN
Uncertain
0.56
D
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.9
L
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-0.55
N
REVEL
Benign
0.17
Sift
Uncertain
0.0090
D
Sift4G
Uncertain
0.038
D
Polyphen
0.99
D
Vest4
0.48
MutPred
0.67
Loss of sheet (P = 0.0315);
MVP
0.27
MPC
0.99
ClinPred
0.87
D
GERP RS
4.1
Varity_R
0.12
gMVP
0.95

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.

Other links and lift over

hg19: chr19-46215310; API