17-39281439-T-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000264658.11(FBXL20):ā€‹c.646A>Gā€‹(p.Ile216Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,461,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.000016 ( 0 hom. )

Consequence

FBXL20
ENST00000264658.11 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.67
Variant links:
Genes affected
FBXL20 (HGNC:24679): (F-box and leucine rich repeat protein 20) Members of the F-box protein family, such as FBXL20, 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 Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.1740017).
BS2
High AC in GnomAdExome4 at 23 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FBXL20NM_032875.3 linkuse as main transcriptc.646A>G p.Ile216Val missense_variant 9/15 ENST00000264658.11 NP_116264.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FBXL20ENST00000264658.11 linkuse as main transcriptc.646A>G p.Ile216Val missense_variant 9/151 NM_032875.3 ENSP00000264658 P1Q96IG2-1
FBXL20ENST00000394294.7 linkuse as main transcriptc.550A>G p.Ile184Val missense_variant 8/141 ENSP00000377832 Q96IG2-2
FBXL20ENST00000577399.5 linkuse as main transcriptc.652A>G p.Ile218Val missense_variant 9/155 ENSP00000462878
FBXL20ENST00000583610.5 linkuse as main transcriptc.646A>G p.Ile216Val missense_variant 9/162 ENSP00000462271 P1Q96IG2-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000319
AC:
8
AN:
250790
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135538
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 SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000157
AC:
23
AN:
1461414
Hom.:
0
Cov.:
30
AF XY:
0.0000206
AC XY:
15
AN XY:
727018
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:
0.000128
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.00000899
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756
ExAC
AF:
0.0000165
AC:
2

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 GeneticsJun 01, 2023The c.646A>G (p.I216V) alteration is located in exon 9 (coding exon 9) of the FBXL20 gene. This alteration results from a A to G substitution at nucleotide position 646, causing the isoleucine (I) at amino acid position 216 to be replaced by a valine (V). 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
0.078
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.24
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Benign
0.16
T;T;.;T
Eigen
Benign
0.074
Eigen_PC
Uncertain
0.28
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.91
.;D;D;D
M_CAP
Benign
0.0082
T
MetaRNN
Benign
0.17
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.87
L;L;.;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-0.64
N;.;N;.
REVEL
Benign
0.16
Sift
Benign
0.30
T;.;T;.
Sift4G
Benign
0.58
T;T;T;T
Polyphen
0.021
B;B;B;.
Vest4
0.38
MutPred
0.41
Gain of helix (P = 0.062);Gain of helix (P = 0.062);.;.;
MVP
0.40
MPC
0.75
ClinPred
0.12
T
GERP RS
5.9
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.6
Varity_R
0.14
gMVP
0.54

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs750700672; hg19: chr17-37437692; API