19-38942691-C-T

Variant names:

• chr19-38942691-C-T
• rs758784059
• NM_024907.7:c.754G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.22
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.347641).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024907.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO17	NM_024907.7	MANE Select	c.754G>A	p.Gly252Arg	missense	Exon 6 of 6	NP_079183.4
	FBXO17	NM_148169.3		c.781G>A	p.Gly261Arg	missense	Exon 6 of 6	NP_680474.1
	FBXO17	NR_104026.2		n.966G>A		non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO17	ENST00000292852.9	TSL:1 MANE Select	c.754G>A	p.Gly252Arg	missense	Exon 6 of 6	ENSP00000292852.3	Q96EF6
	ENSG00000269547	ENST00000599996.1	TSL:2	c.466G>A	p.Gly156Arg	missense	Exon 5 of 20	ENSP00000472465.1	M0R2C6
	FBXO17	ENST00000939441.1		c.796G>A	p.Gly266Arg	missense	Exon 6 of 6	ENSP00000609500.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.0000333 AC: 8 AN: 240120 AF XY: 0.0000460

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000644

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000199 AC: 29 AN: 1453696 Hom.: 1 Cov.: 34 AF XY: 0.0000194 AC XY: 14 AN XY: 723144

African (AFR) AF: 0.00 AC: 0 AN: 32728

American (AMR) AF: 0.0000231 AC: 1 AN: 43358

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25902

East Asian (EAS) AF: 0.00 AC: 0 AN: 38750

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53358

Middle Eastern (MID) AF: 0.000348 AC: 2 AN: 5748

European-Non Finnish (NFE) AF: 0.0000225 AC: 25 AN: 1108904

Other (OTH) AF: 0.00 AC: 0 AN: 60112

GnomAD4 genome Cov.: 34

Alfa AF: 0.0000624 Hom.: 0

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.096
FATHMM_MKL	Benign	0.32	N
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.48	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		2.2
PROVEAN	Pathogenic	-6.2	D
REVEL	Benign	0.16
Sift	Uncertain	0.026	D
Sift4G	Uncertain	0.029	D
Polyphen		0.94	P
Vest4		0.51
MVP		0.53
MPC		1.1
ClinPred		0.82	D
GERP RS		3.7
Varity_R		0.15
gMVP		0.70
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

dbSNP: rs758784059; hg19: chr19-39433331;