Variant 7-102883467-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001394494.2(FBXL13):c.1496G>A(p.Gly499Glu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000658 in 151,866 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

FBXL13
NM_001394494.2 missense, splice_region

Scores

Splicing: ADA: 0.9990

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.93

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]

FBXL13 links:

FBXL13 (HGNC:):

FBXL13 links:

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/exons	Protein	UniProt
FBXL13	NM_001394494.2 linkuse as main transcript	c.1496G>A	p.Gly499Glu	missense_variant, splice_region_variant	15/21	NP_001381423.1
FBXL13	NM_145032.3 linkuse as main transcript	c.1226G>A	p.Gly409Glu	missense_variant, splice_region_variant	14/20	NP_659469.3	Q8NEE6-1Q8N1P0
FBXL13	NM_001287150.2 linkuse as main transcript	c.1226G>A	p.Gly409Glu	missense_variant, splice_region_variant	14/19	NP_001274079.1	Q8NEE6-2Q8N1P0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXL13	ENST00000440067.4 linkuse as main transcript	c.1496G>A	p.Gly499Glu	missense_variant, splice_region_variant	15/21	3		ENSP00000390126.2		C9JI88

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151866

Hom.:

Cov.:

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:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000413

AC:

AN:

242400

Hom.:

AF XY:

0.00

AC XY:

AN XY:

130948

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000558

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151866

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74134

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Oct 03, 2022

The c.1226G>A (p.G409E) alteration is located in exon 14 (coding exon 12) of the FBXL13 gene. This alteration results from a G to A substitution at nucleotide position 1226, causing the glycine (G) at amino acid position 409 to be replaced by a glutamic acid (E). 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

Pathogenic

0.76

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.059

.;T;T;.;.

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.86

D;.;D;D;D

M_CAP

Benign

0.038

MetaRNN

Uncertain

0.72

D;D;D;D;D

MetaSVM

Benign

-0.28

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-4.9

D;D;D;.;D

REVEL

Uncertain

0.43

Sift

Benign

0.052

T;D;D;.;T

Sift4G

Uncertain

0.049

D;T;T;D;D

Polyphen

1.0

D;D;D;.;D

Vest4

0.69

MutPred

0.49

Loss of MoRF binding (P = 0.0127);Loss of MoRF binding (P = 0.0127);Loss of MoRF binding (P = 0.0127);.;Loss of MoRF binding (P = 0.0127);

MVP

0.74

MPC

0.56

ClinPred

0.99

GERP RS

5.3

Varity_R

0.69

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.92

SpliceAI score (max)

0.12

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over