chr3-196584190-C-T

Variant summary

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

The NM_001105573.2(FBXO45):​c.733C>T​(p.Arg245Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,612 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

FBXO45
NM_001105573.2 missense

Scores

10
5
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.92
Variant links:
Genes affected
FBXO45 (HGNC:29148): (F-box protein 45) Members of the F-box protein family, such as FBXO45, 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 (summary by Jin et al., 2004 [PubMed 15520277]).[supplied by OMIM, Jan 2011]

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
FBXO45NM_001105573.2 linkc.733C>T p.Arg245Cys missense_variant Exon 3 of 3 ENST00000311630.7 NP_001099043.1 P0C2W1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FBXO45ENST00000311630.7 linkc.733C>T p.Arg245Cys missense_variant Exon 3 of 3 1 NM_001105573.2 ENSP00000310332.6 P0C2W1
FBXO45ENST00000440469.1 linkc.196C>T p.Arg66Cys missense_variant Exon 3 of 3 2 ENSP00000389868.1 C9JLC0

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461612
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727082
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
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
Feb 06, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.733C>T (p.R245C) alteration is located in exon 3 (coding exon 3) of the FBXO45 gene. This alteration results from a C to T substitution at nucleotide position 733, causing the arginine (R) at amino acid position 245 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
Pathogenic
0.98
BayesDel_addAF
Pathogenic
0.31
D
BayesDel_noAF
Pathogenic
0.21
CADD
Pathogenic
32
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.18
T;D
Eigen
Pathogenic
0.73
Eigen_PC
Pathogenic
0.68
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Pathogenic
0.99
D;D
M_CAP
Benign
0.074
D
MetaRNN
Uncertain
0.72
D;D
MetaSVM
Uncertain
-0.16
T
MutationAssessor
Pathogenic
2.9
.;M
PrimateAI
Pathogenic
0.88
D
PROVEAN
Pathogenic
-4.7
D;D
REVEL
Uncertain
0.42
Sift
Benign
0.070
T;T
Sift4G
Uncertain
0.031
D;D
Polyphen
1.0
.;D
Vest4
0.67
MutPred
0.65
.;Gain of glycosylation at T240 (P = 0.0891);
MVP
0.88
MPC
2.6
ClinPred
1.0
D
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.41
gMVP
0.74

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: chr3-196311061; API