NM_018994.3:c.1373G>T

Variant summary

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

The NM_018994.3(FBXO42):​c.1373G>T​(p.Ser458Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

FBXO42
NM_018994.3 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.83
Variant links:
Genes affected
FBXO42 (HGNC:29249): (F-box protein 42) Members of the F-box protein family, such as FBXO42, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (SKP1A; 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, Dec 2010]

Genome browser will be placed here

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=0.20830923).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FBXO42NM_018994.3 linkc.1373G>T p.Ser458Ile missense_variant Exon 10 of 10 ENST00000375592.8 NP_061867.1 Q6P3S6
FBXO42XM_047422747.1 linkc.1373G>T p.Ser458Ile missense_variant Exon 12 of 12 XP_047278703.1
FBXO42XM_047422750.1 linkc.1373G>T p.Ser458Ile missense_variant Exon 12 of 12 XP_047278706.1
FBXO42XM_047422751.1 linkc.1373G>T p.Ser458Ile missense_variant Exon 12 of 12 XP_047278707.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FBXO42ENST00000375592.8 linkc.1373G>T p.Ser458Ile missense_variant Exon 10 of 10 1 NM_018994.3 ENSP00000364742.3 Q6P3S6
FBXO42ENST00000444116.1 linkc.527G>T p.Ser176Ile missense_variant Exon 4 of 4 5 ENSP00000412416.1 X6RKU3
FBXO42ENST00000456164.5 linkc.527G>T p.Ser176Ile missense_variant Exon 3 of 3 2 ENSP00000415663.1 X6RKU3

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152152
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
33
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152152
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74336
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 20, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1373G>T (p.S458I) alteration is located in exon 10 (coding exon 9) of the FBXO42 gene. This alteration results from a G to T substitution at nucleotide position 1373, causing the serine (S) at amino acid position 458 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
0.24
BayesDel_addAF
Uncertain
0.096
D
BayesDel_noAF
Benign
-0.10
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.021
T;T;T
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.78
T;.;T
M_CAP
Benign
0.056
D
MetaRNN
Benign
0.21
T;T;T
MetaSVM
Benign
-0.84
T
MutationAssessor
Benign
1.6
L;.;.
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-1.4
N;N;N
REVEL
Benign
0.14
Sift
Uncertain
0.023
D;D;D
Sift4G
Uncertain
0.058
T;.;.
Polyphen
0.98
D;.;.
Vest4
0.40
MutPred
0.32
Loss of sheet (P = 0.0037);.;.;
MVP
0.36
MPC
0.39
ClinPred
0.70
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.28
gMVP
0.60

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: rs1403564631; hg19: chr1-16577946; API