7-102883464-T-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001394494.2(FBXL13):āc.1499A>Gā(p.Asn500Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000997 in 1,604,998 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 (ā ).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 31)
Exomes š: 0.0000096 ( 0 hom. )
Consequence
FBXL13
NM_001394494.2 missense
NM_001394494.2 missense
Scores
5
13
Clinical Significance
Conservation
PhyloP100: 3.03
Genes affected
FBXL13 (HGNC:21658): (F-box and leucine rich repeat protein 13) Members of the F-box protein family, such as FBXL13, 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 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.113681644).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FBXL13 | NM_001394494.2 | c.1499A>G | p.Asn500Ser | missense_variant | 15/21 | NP_001381423.1 | ||
FBXL13 | NM_145032.3 | c.1229A>G | p.Asn410Ser | missense_variant | 14/20 | NP_659469.3 | ||
FBXL13 | NM_001287150.2 | c.1229A>G | p.Asn410Ser | missense_variant | 14/19 | NP_001274079.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152068Hom.: 0 Cov.: 31
GnomAD3 genomes
AF:
AC:
2
AN:
152068
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000495 AC: 12AN: 242434Hom.: 0 AF XY: 0.0000382 AC XY: 5AN XY: 131000
GnomAD3 exomes
AF:
AC:
12
AN:
242434
Hom.:
AF XY:
AC XY:
5
AN XY:
131000
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000964 AC: 14AN: 1452812Hom.: 0 Cov.: 30 AF XY: 0.0000125 AC XY: 9AN XY: 722102
GnomAD4 exome
AF:
AC:
14
AN:
1452812
Hom.:
Cov.:
30
AF XY:
AC XY:
9
AN XY:
722102
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152186Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74402
GnomAD4 genome
AF:
AC:
2
AN:
152186
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
74402
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
ExAC
AF:
AC:
4
Asia WGS
AF:
AC:
1
AN:
3478
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 10, 2023 | The c.1229A>G (p.N410S) alteration is located in exon 14 (coding exon 12) of the FBXL13 gene. This alteration results from a A to G substitution at nucleotide position 1229, causing the asparagine (N) at amino acid position 410 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;.;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;.;D
REVEL
Benign
Sift
Benign
D;D;D;.;T
Sift4G
Benign
T;T;T;T;T
Polyphen
D;D;D;.;D
Vest4
MutPred
Gain of phosphorylation at N410 (P = 0.0337);Gain of phosphorylation at N410 (P = 0.0337);Gain of phosphorylation at N410 (P = 0.0337);.;Gain of phosphorylation at N410 (P = 0.0337);
MVP
MPC
0.43
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at