19-38942655-C-A

Variant summary

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

The NM_024907.7(FBXO17):​c.790G>T​(p.Ala264Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,447,126 control chromosomes in the GnomAD database, with no homozygous occurrence. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A264T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

FBXO17
NM_024907.7 missense

Scores

2
14

Clinical Significance

Not reported in ClinVar

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]

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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
FBXO17NM_024907.7 linkc.790G>T p.Ala264Ser missense_variant Exon 6 of 6 ENST00000292852.9 NP_079183.4 Q96EF6
FBXO17NM_148169.3 linkc.817G>T p.Ala273Ser missense_variant Exon 6 of 6 NP_680474.1 Q96EF6
FBXO17NR_104026.2 linkn.1002G>T 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>T p.Ala264Ser missense_variant Exon 6 of 6 1 NM_024907.7 ENSP00000292852.3 Q96EF6
ENSG00000269547ENST00000599996.1 linkc.474+28G>T intron_variant Intron 5 of 19 2 ENSP00000472465.1 M0R2C6

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.91e-7
AC:
1
AN:
1447126
Hom.:
0
Cov.:
29
AF XY:
0.00000139
AC XY:
1
AN XY:
719952
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:
0.0000188
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
18
DANN
Uncertain
0.98
DEOGEN2
Benign
0.039
T;T
Eigen
Benign
-0.46
Eigen_PC
Benign
-0.43
FATHMM_MKL
Benign
0.47
N
M_CAP
Benign
0.0054
T
MetaRNN
Uncertain
0.44
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.38
N;N
PROVEAN
Benign
-1.1
N;.
REVEL
Benign
0.076
Sift
Benign
0.13
T;.
Sift4G
Benign
0.55
T;T
Polyphen
0.47
P;P
Vest4
0.13
MutPred
0.82
Gain of disorder (P = 0.0242);Gain of disorder (P = 0.0242);
MVP
0.26
MPC
0.57
ClinPred
0.42
T
GERP RS
2.6
Varity_R
0.050
gMVP
0.18

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-39433295; COSMIC: COSV99494343; COSMIC: COSV99494343; API