1-16251211-T-C

Variant summary

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

The NM_018994.3(FBXO42):​c.1613A>G​(p.His538Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,878 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: 0.0000027 ( 0 hom. )

Consequence

FBXO42
NM_018994.3 missense

Scores

4
7
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.17
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 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
FBXO42NM_018994.3 linkc.1613A>G p.His538Arg missense_variant Exon 10 of 10 ENST00000375592.8 NP_061867.1 Q6P3S6
FBXO42XM_047422747.1 linkc.1613A>G p.His538Arg missense_variant Exon 12 of 12 XP_047278703.1
FBXO42XM_047422750.1 linkc.1613A>G p.His538Arg missense_variant Exon 12 of 12 XP_047278706.1
FBXO42XM_047422751.1 linkc.1613A>G p.His538Arg 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.1613A>G p.His538Arg missense_variant Exon 10 of 10 1 NM_018994.3 ENSP00000364742.3 Q6P3S6
FBXO42ENST00000444116.1 linkc.767A>G p.His256Arg missense_variant Exon 4 of 4 5 ENSP00000412416.1 X6RKU3
FBXO42ENST00000456164.5 linkc.767A>G p.His256Arg missense_variant Exon 3 of 3 2 ENSP00000415663.1 X6RKU3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251208
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135794
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461878
Hom.:
0
Cov.:
30
AF XY:
0.00000413
AC XY:
3
AN XY:
727240
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:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 14, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1613A>G (p.H538R) alteration is located in exon 10 (coding exon 9) of the FBXO42 gene. This alteration results from a A to G substitution at nucleotide position 1613, causing the histidine (H) at amino acid position 538 to be replaced by an arginine (R). 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
Uncertain
0.52
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.020
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.062
T;T;T
Eigen
Uncertain
0.56
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.90
D;.;D
M_CAP
Benign
0.042
D
MetaRNN
Uncertain
0.46
T;T;T
MetaSVM
Benign
-0.61
T
MutationAssessor
Benign
0.90
L;.;.
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
-2.0
N;N;N
REVEL
Benign
0.20
Sift
Pathogenic
0.0
D;D;D
Sift4G
Benign
0.35
T;.;.
Polyphen
0.98
D;.;.
Vest4
0.60
MutPred
0.35
Gain of sheet (P = 0.0036);.;.;
MVP
0.49
MPC
0.99
ClinPred
0.80
D
GERP RS
5.5
Varity_R
0.40
gMVP
0.50

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: rs780501004; hg19: chr1-16577706; API