19-38942655-C-T

Variant summary

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

The NM_024907.7(FBXO17):​c.790G>A​(p.Ala264Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000713 in 1,599,284 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000076 ( 2 hom. )

Consequence

FBXO17
NM_024907.7 missense

Scores

2
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.42
Variant links:
Genes affected
FBXO17 (HGNC:18754): (F-box protein 17) This gene encodes a member of the F-box protein family which is characterized by the F-box motif. The F-box proteins constitute one of the four subunits of the 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 Fbxs class and it contains an F-box domain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

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=0.095864266).
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FBXO17NM_024907.7 linkc.790G>A p.Ala264Thr missense_variant Exon 6 of 6 ENST00000292852.9 NP_079183.4 Q96EF6
FBXO17NM_148169.3 linkc.817G>A p.Ala273Thr missense_variant Exon 6 of 6 NP_680474.1 Q96EF6
FBXO17NR_104026.2 linkn.1002G>A non_coding_transcript_exon_variant Exon 6 of 6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FBXO17ENST00000292852.9 linkc.790G>A p.Ala264Thr missense_variant Exon 6 of 6 1 NM_024907.7 ENSP00000292852.3 Q96EF6
ENSG00000269547ENST00000599996.1 linkc.474+28G>A intron_variant Intron 5 of 19 2 ENSP00000472465.1 M0R2C6

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152158
Hom.:
0
Cov.:
31
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:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000855
AC:
20
AN:
233804
Hom.:
0
AF XY:
0.000110
AC XY:
14
AN XY:
127294
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000324
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000665
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000760
AC:
110
AN:
1447126
Hom.:
2
Cov.:
29
AF XY:
0.0000875
AC XY:
63
AN XY:
719952
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000238
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000526
Gnomad4 SAS exome
AF:
0.000667
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000434
Gnomad4 OTH exome
AF:
0.0000501
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152158
Hom.:
0
Cov.:
31
AF XY:
0.0000404
AC XY:
3
AN XY:
74340
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:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000189
ExAC
AF:
0.0000906
AC:
11

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 18, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.817G>A (p.A273T) alteration is located in exon 6 (coding exon 6) of the FBXO17 gene. This alteration results from a G to A substitution at nucleotide position 817, causing the alanine (A) at amino acid position 273 to be replaced by a threonine (T). 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
0.23
BayesDel_addAF
Benign
-0.46
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.043
T;T
Eigen
Benign
-0.71
Eigen_PC
Benign
-0.61
FATHMM_MKL
Benign
0.40
N
M_CAP
Benign
0.0040
T
MetaRNN
Benign
0.096
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.1
M;M
PROVEAN
Benign
-1.2
N;.
REVEL
Benign
0.064
Sift
Benign
0.058
T;.
Sift4G
Benign
0.66
T;T
Polyphen
0.012
B;B
Vest4
0.11
MutPred
0.73
Loss of stability (P = 0.0877);Loss of stability (P = 0.0877);
MVP
0.24
MPC
0.35
ClinPred
0.063
T
GERP RS
2.6
Varity_R
0.044
gMVP
0.19

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs781330255; hg19: chr19-39433295; API