Genetic Variant FBXO17:p.Gly252Arg (chr19-38942691-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

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

The NM_024907.7(FBXO17):c.754G>A(p.Gly252Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 1,453,696 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.000020 ( 1 hom. )

Consequence

FBXO17
NM_024907.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.22

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]

FBXO17 links:

ENSG00000269547 (HGNC:):

ENSG00000269547 links:

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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=0.347641).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXO17	NM_024907.7 link	c.754G>A	p.Gly252Arg	missense_variant	Exon 6 of 6	ENST00000292852.9	NP_079183.4	Q96EF6
FBXO17	NM_148169.3 link	c.781G>A	p.Gly261Arg	missense_variant	Exon 6 of 6		NP_680474.1	Q96EF6
FBXO17	NR_104026.2 link	n.966G>A		non_coding_transcript_exon_variant	Exon 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXO17	ENST00000292852.9 link	c.754G>A	p.Gly252Arg	missense_variant	Exon 6 of 6	1	NM_024907.7	ENSP00000292852.3		Q96EF6
ENSG00000269547	ENST00000599996.1 link	c.466G>A	p.Gly156Arg	missense_variant	Exon 5 of 20	2		ENSP00000472465.1		M0R2C6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000333

AC:

AN:

240120

Hom.:

AF XY:

0.0000460

AC XY:

AN XY:

130394

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:

0.0000341

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000644

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000199

AC:

AN:

1453696

Hom.:

Cov.:

AF XY:

0.0000194

AC XY:

AN XY:

723144

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000231

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000225

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000624

Hom.:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 26, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.781G>A (p.G261R) 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 781, causing the glycine (G) at amino acid position 261 to be replaced by an arginine (R). 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

Pathogenic

0.92

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.32

T;T

Eigen

Benign

0.15

Eigen_PC

Benign

0.096

FATHMM_MKL

Benign

0.32

M_CAP

Benign

0.037

MetaRNN

Benign

0.35

T;T

MetaSVM

Benign

-0.48

MutationAssessor

Pathogenic

3.0

M;M

PROVEAN

Pathogenic

-6.2

D;.

REVEL

Benign

0.16

Sift

Uncertain

0.026

D;.

Sift4G

Uncertain

0.029

D;D

Polyphen

0.94

P;P

Vest4

0.51

MVP

0.53

MPC

1.1

ClinPred

0.82

GERP RS

3.7

Varity_R

0.15

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over