rs781733633

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The ENST00000440067.4(FBXL13):​c.1951G>C​(p.Val651Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000486 in 1,439,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

FBXL13
ENST00000440067.4 missense

Scores

18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.184

Publications

0 publications found
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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.058544695).
BP6
Variant 7-102854815-C-G is Benign according to our data. Variant chr7-102854815-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2492878.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FBXL13NM_001394494.2 linkc.1951G>C p.Val651Leu missense_variant Exon 18 of 21 NP_001381423.1
FBXL13NM_145032.3 linkc.1681G>C p.Val561Leu missense_variant Exon 17 of 20 NP_659469.3 Q8NEE6-1Q8N1P0
FBXL13NM_001111038.2 linkc.1681G>C p.Val561Leu missense_variant Exon 17 of 19 NP_001104508.1 Q8NEE6-3Q8N1P0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FBXL13ENST00000440067.4 linkc.1951G>C p.Val651Leu missense_variant Exon 18 of 21 3 ENSP00000390126.2 C9JI88

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000409
AC:
1
AN:
244648
AF XY:
0.00000754
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 FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000895
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000486
AC:
7
AN:
1439546
Hom.:
0
Cov.:
26
AF XY:
0.00000419
AC XY:
3
AN XY:
716578
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
32832
American (AMR)
AF:
0.00
AC:
0
AN:
42684
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25774
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39134
South Asian (SAS)
AF:
0.00
AC:
0
AN:
82798
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52942
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5660
European-Non Finnish (NFE)
AF:
0.00000546
AC:
6
AN:
1098196
Other (OTH)
AF:
0.0000168
AC:
1
AN:
59526
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000825
AC:
1

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Mar 01, 2023
Ambry Genetics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
2.1
DANN
Benign
0.64
DEOGEN2
Benign
0.00018
T;T;.;.
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.080
N
LIST_S2
Benign
0.68
.;T;T;T
M_CAP
Benign
0.0019
T
MetaRNN
Benign
0.059
T;T;T;T
MetaSVM
Benign
-0.92
T
PhyloP100
-0.18
PrimateAI
Benign
0.29
T
PROVEAN
Benign
0.23
N;N;.;N
REVEL
Benign
0.017
Sift
Benign
1.0
T;T;.;T
Sift4G
Benign
0.98
T;T;T;T
Polyphen
0.0010
B;B;.;B
Vest4
0.068
MutPred
0.41
Gain of disorder (P = 0.1522);Gain of disorder (P = 0.1522);.;Gain of disorder (P = 0.1522);
MVP
0.13
MPC
0.091
ClinPred
0.010
T
GERP RS
-3.5
Varity_R
0.048
gMVP
0.22
Mutation Taster
=94/6
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs781733633; hg19: chr7-102495262; API