rs751465472

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001394494.2(FBXL13):​c.1753G>T​(p.Ala585Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A585T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

FBXL13
NM_001394494.2 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.16
Variant links:
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06736535).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FBXL13NM_001394494.2 linkc.1753G>T p.Ala585Ser missense_variant Exon 16 of 21 NP_001381423.1
FBXL13NM_145032.3 linkc.1483G>T p.Ala495Ser missense_variant Exon 15 of 20 NP_659469.3 Q8NEE6-1Q8N1P0
FBXL13NM_001287150.2 linkc.1483G>T p.Ala495Ser missense_variant Exon 15 of 19 NP_001274079.1 Q8NEE6-2Q8N1P0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FBXL13ENST00000440067.4 linkc.1753G>T p.Ala585Ser missense_variant Exon 16 of 21 3 ENSP00000390126.2 C9JI88

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.87e-7
AC:
1
AN:
1454696
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
723496
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:
9.02e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.085
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
0.020
DANN
Benign
0.44
DEOGEN2
Benign
0.0029
.;T;T;.;.
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.042
N
LIST_S2
Benign
0.43
T;.;T;T;T
M_CAP
Benign
0.0022
T
MetaRNN
Benign
0.067
T;T;T;T;T
MetaSVM
Benign
-0.93
T
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-1.2
N;N;N;.;N
REVEL
Benign
0.018
Sift
Benign
0.62
T;T;T;.;T
Sift4G
Benign
0.59
T;T;T;T;T
Polyphen
0.0030
B;B;B;.;B
Vest4
0.30
MutPred
0.41
Gain of disorder (P = 0.0088);Gain of disorder (P = 0.0088);Gain of disorder (P = 0.0088);.;Gain of disorder (P = 0.0088);
MVP
0.085
MPC
0.086
ClinPred
0.030
T
GERP RS
-4.3
Varity_R
0.043
gMVP
0.22

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: chr7-102518803; API