5-171869779-C-T

Variant summary

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

The NM_001378974.1(FBXW11):​c.1480G>A​(p.Ala494Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,238 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

FBXW11
NM_001378974.1 missense

Scores

7
7
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.86
Variant links:
Genes affected
FBXW11 (HGNC:13607): (F-box and WD repeat domain containing 11) This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbws class and, in addition to an F-box, contains multiple WD40 repeats. This gene contains at least 14 exons, and its alternative splicing generates 3 transcript variants diverging at the presence/absence of two alternate exons. [provided by RefSeq, Jul 2008]

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 rank MANE Protein UniProt
FBXW11NM_001378974.1 linkc.1480G>A p.Ala494Thr missense_variant Exon 12 of 14 ENST00000517395.6 NP_001365903.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FBXW11ENST00000517395.6 linkc.1480G>A p.Ala494Thr missense_variant Exon 12 of 14 3 NM_001378974.1 ENSP00000428753.2 E5RGC1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1458238
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
725220
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Neurodevelopmental, jaw, eye, and digital syndrome Uncertain:1
Nov 25, 2020
Institute of Human Genetics, University of Goettingen
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.030
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.31
.;T;.
Eigen
Pathogenic
0.70
Eigen_PC
Pathogenic
0.74
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
1.0
D;D;D
M_CAP
Benign
0.038
D
MetaRNN
Uncertain
0.67
D;D;D
MetaSVM
Benign
-0.47
T
MutationAssessor
Benign
1.2
.;L;.
PrimateAI
Pathogenic
0.88
D
PROVEAN
Uncertain
-3.2
D;D;D
REVEL
Uncertain
0.43
Sift
Uncertain
0.0020
D;D;D
Sift4G
Uncertain
0.0070
D;D;D
Polyphen
1.0
D;D;D
Vest4
0.68
MutPred
0.56
.;Gain of sheet (P = 0.1539);.;
MVP
0.52
MPC
2.4
ClinPred
0.96
D
GERP RS
5.5
Varity_R
0.79
gMVP
0.47

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs1310419699; hg19: chr5-171296783; API