7-102813460-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000440067.4(FBXL13):​c.2360T>A​(p.Phe787Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,614,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

FBXL13
ENST00000440067.4 missense

Scores

7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.94
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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.297884).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FBXL13NM_001394494.2 linkuse as main transcriptc.2360T>A p.Phe787Tyr missense_variant 21/21 ENST00000440067.4 NP_001381423.1
FBXL13NR_105043.2 linkuse as main transcriptn.2309T>A non_coding_transcript_exon_variant 21/21

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FBXL13ENST00000440067.4 linkuse as main transcriptc.2360T>A p.Phe787Tyr missense_variant 21/213 NM_001394494.2 ENSP00000390126 P2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152168
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
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
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461866
Hom.:
0
Cov.:
30
AF XY:
0.00000413
AC XY:
3
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152168
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
EpiCase
AF:
0.0000545
EpiControl
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 submitterclinical testingAmbry GeneticsApr 04, 2024The c.2090T>A (p.F697Y) alteration is located in exon 20 (coding exon 18) of the FBXL13 gene. This alteration results from a T to A substitution at nucleotide position 2090, causing the phenylalanine (F) at amino acid position 697 to be replaced by a tyrosine (Y). 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
Benign
0.24
BayesDel_addAF
Benign
-0.081
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
18
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0031
.;T;T;.;.
Eigen
Uncertain
0.45
Eigen_PC
Uncertain
0.42
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.70
T;.;T;T;T
M_CAP
Benign
0.0069
T
MetaRNN
Benign
0.30
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
0.57
D;D;N;N;N;N;N;N
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-1.2
N;N;N;N;N
REVEL
Benign
0.13
Sift
Uncertain
0.0030
D;D;D;D;D
Sift4G
Uncertain
0.029
D;D;D;D;D
Polyphen
0.95
P;P;P;D;D
Vest4
0.37
MutPred
0.36
.;Gain of disorder (P = 0.0857);Gain of disorder (P = 0.0857);.;.;
MVP
0.24
MPC
0.13
ClinPred
0.88
D
GERP RS
5.8
Varity_R
0.19
gMVP
0.44

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1797578424; hg19: chr7-102453907; API