19-38942657-C-A

Variant names:

• chr19-38942657-C-A
• NM_024907.7:c.788G>T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_024907.7(FBXO17):​c.788G>T​(p.Gly263Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: FBXO17 NM_024907.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.61

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]

ENSG00000269547 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.974

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXO17	NM_024907.7	c.788G>T	p.Gly263Val	missense_variant	Exon 6 of 6	ENST00000292852.9	NP_079183.4
FBXO17	NM_148169.3	c.815G>T	p.Gly272Val	missense_variant	Exon 6 of 6		NP_680474.1
FBXO17	NR_104026.2	n.1000G>T		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	c.788G>T	p.Gly263Val	missense_variant	Exon 6 of 6	1	NM_024907.7	ENSP00000292852.3
ENSG00000269547	ENST00000599996.1	c.474+26G>T		intron_variant	Intron 5 of 19	2		ENSP00000472465.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.815G>T (p.G272V) alteration is located in exon 6 (coding exon 6) of the FBXO17 gene. This alteration results from a G to T substitution at nucleotide position 815, causing the glycine (G) at amino acid position 272 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	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T;T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Benign	0.59	D
M_CAP	Benign	0.027	D
MetaRNN	Pathogenic	0.97	D;D
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Pathogenic	3.1	M;M
PROVEAN	Pathogenic	-8.0	D;.
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	D;.
Sift4G	Uncertain	0.0090	D;D
Polyphen		1.0	D;D
Vest4		0.72
MutPred		0.87		Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);
MVP		0.55
MPC		1.2
ClinPred		1.0	D
GERP RS		4.7
Varity_R		0.13
gMVP		0.73

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-39433297;