Genetic Variant ENST00000440067.4:c.1673G>C (chr7-102878436-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000440067.4(FBXL13):c.1673G>C(p.Gly558Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FBXL13
ENST00000440067.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.94

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
FBXL13	NM_001394494.2 link	c.1673G>C	p.Gly558Ala	missense_variant	Exon 16 of 21	NP_001381423.1
FBXL13	NM_145032.3 link	c.1403G>C	p.Gly468Ala	missense_variant	Exon 15 of 20	NP_659469.3	Q8NEE6-1Q8N1P0
FBXL13	NM_001287150.2 link	c.1403G>C	p.Gly468Ala	missense_variant	Exon 15 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.1673G>C	p.Gly558Ala	missense_variant	Exon 16 of 21	3		ENSP00000390126.2		C9JI88

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000423

AC:

AN:

236416

AF XY:

0.00000782

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:

0.00000912

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1446626

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719302

African (AFR)

AF:

0.00

AC:

AN:

32820

American (AMR)

AF:

0.00

AC:

AN:

42400

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25824

East Asian (EAS)

AF:

0.00

AC:

AN:

39100

South Asian (SAS)

AF:

0.00

AC:

AN:

82848

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52936

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1105250

Other (OTH)

AF:

0.00

AC:

AN:

59744

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 15, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1403G>C (p.G468A) alteration is located in exon 15 (coding exon 13) of the FBXL13 gene. This alteration results from a G to C substitution at nucleotide position 1403, causing the glycine (G) at amino acid position 468 to be replaced by an alanine (A). 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

Uncertain

0.56

BayesDel_addAF

Uncertain

0.044

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.064

.;T;T;.;.

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.88

D;.;D;D;D

M_CAP

Benign

0.010

MetaRNN

Uncertain

0.62

D;D;D;D;D

MetaSVM

Benign

-1.2

PhyloP100

4.9

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-4.9

D;D;D;.;D

REVEL

Benign

0.21

Sift

Pathogenic

0.0

D;D;D;.;D

Sift4G

Benign

0.14

T;T;T;T;T

Polyphen

1.0

D;D;D;.;D

Vest4

0.62

MutPred

0.48

Gain of catalytic residue at G468 (P = 0.0416);Gain of catalytic residue at G468 (P = 0.0416);Gain of catalytic residue at G468 (P = 0.0416);.;Gain of catalytic residue at G468 (P = 0.0416);

MVP

0.23

MPC

0.51

ClinPred

0.99

GERP RS

5.4

Varity_R

0.85

gMVP

0.70

Mutation Taster

=66/34

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over