chr7-102883467-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The ENST00000440067.4(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
ENST00000440067.4 missense, splice_region

Scores

Splicing: ADA: 0.9990

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.93

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]

FBXL13 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
FBXL13	NM_001394494.2 link	c.1496G>A	p.Gly499Glu	missense_variant, splice_region_variant	Exon 15 of 21	NP_001381423.1
FBXL13	NM_145032.3 link	c.1226G>A	p.Gly409Glu	missense_variant, splice_region_variant	Exon 14 of 20	NP_659469.3	Q8NEE6-1Q8N1P0
FBXL13	NM_001287150.2 link	c.1226G>A	p.Gly409Glu	missense_variant, splice_region_variant	Exon 14 of 19	NP_001274079.1	Q8NEE6-2Q8N1P0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXL13	ENST00000440067.4 link	c.1496G>A	p.Gly499Glu	missense_variant, splice_region_variant	Exon 15 of 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

GnomAD2 exomes

AF:

0.00000413

AC:

AN:

242400

AF XY:

0.00

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 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

African (AFR)

AF:

0.00

AC:

AN:

41330

American (AMR)

AF:

0.00

AC:

AN:

15206

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67980

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 03, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

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

PhyloP100

3.9

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

Mutation Taster

=35/65

disease causing

(source)

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

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chr7-102883467-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over