1-16250846-C-T

Variant summary

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

The NM_018994.3(FBXO42):​c.1978G>A​(p.Val660Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000632 in 1,614,038 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 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000068 ( 0 hom. )

Consequence

FBXO42
NM_018994.3 missense

Scores

3
4
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.65
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.29733416).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FBXO42NM_018994.3 linkc.1978G>A p.Val660Ile missense_variant Exon 10 of 10 ENST00000375592.8 NP_061867.1 Q6P3S6
FBXO42XM_047422747.1 linkc.1978G>A p.Val660Ile missense_variant Exon 12 of 12 XP_047278703.1
FBXO42XM_047422750.1 linkc.1978G>A p.Val660Ile missense_variant Exon 12 of 12 XP_047278706.1
FBXO42XM_047422751.1 linkc.1978G>A p.Val660Ile 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.1978G>A p.Val660Ile missense_variant Exon 10 of 10 1 NM_018994.3 ENSP00000364742.3 Q6P3S6
FBXO42ENST00000444116.1 linkc.*236G>A downstream_gene_variant 5 ENSP00000412416.1 X6RKU3
FBXO42ENST00000456164.5 linkc.*236G>A downstream_gene_variant 2 ENSP00000415663.1 X6RKU3

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152144
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000358
AC:
9
AN:
251490
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135918
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:
0.0000791
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000677
AC:
99
AN:
1461894
Hom.:
0
Cov.:
30
AF XY:
0.0000756
AC XY:
55
AN XY:
727248
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:
0.0000872
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152144
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
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:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000772
Hom.:
0
Bravo
AF:
0.0000264
ExAC
AF:
0.0000659
AC:
8
EpiCase
AF:
0.000164
EpiControl
AF:
0.000178

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 28, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1978G>A (p.V660I) alteration is located in exon 10 (coding exon 9) of the FBXO42 gene. This alteration results from a G to A substitution at nucleotide position 1978, causing the valine (V) at amino acid position 660 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
0.28
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.34
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.043
T
Eigen
Uncertain
0.64
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.87
D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.30
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.69
N
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-0.22
N
REVEL
Benign
0.18
Sift
Pathogenic
0.0
D
Sift4G
Benign
0.52
T
Polyphen
0.98
D
Vest4
0.39
MVP
0.33
MPC
0.79
ClinPred
0.37
T
GERP RS
5.5
Varity_R
0.36
gMVP
0.49

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: rs772674017; hg19: chr1-16577341; API