chr19-38949974-C-G

Variant names:

• chr19-38949974-C-G
• rs751710358
• NM_024907.7:c.346G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024907.7(FBXO17):​c.346G>C​(p.Glu116Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 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. E116D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: FBXO17 NM_024907.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.343
• 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]

ENSG00000305395 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11211896).

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.346G>C	p.Glu116Gln	missense	Exon 2 of 6	NP_079183.4
	FBXO17	NM_148169.3		c.373G>C	p.Glu125Gln	missense	Exon 2 of 6	NP_680474.1
	FBXO17	NR_104026.2		n.520G>C		non_coding_transcript_exon	Exon 2 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO17	ENST00000292852.9	TSL:1 MANE Select	c.346G>C	p.Glu116Gln	missense	Exon 2 of 6	ENSP00000292852.3	Q96EF6
	FBXO17	ENST00000939441.1		c.346G>C	p.Glu116Gln	missense	Exon 2 of 6	ENSP00000609500.1
	FBXO17	ENST00000595329.5	TSL:2	c.346G>C	p.Glu116Gln	missense	Exon 2 of 6	ENSP00000470361.1	Q96EF6

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.53	D
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.34
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.062
Sift	Benign	0.47	T
Sift4G	Benign	0.45	T
Polyphen		0.43	B
Vest4		0.15
MutPred		0.58		Loss of catalytic residue at E116 (P = 0.0842)
MVP		0.43
MPC		0.56
ClinPred		0.18	T
GERP RS		2.8
PromoterAI		-0.048	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.054
gMVP		0.23
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs751710358; hg19: chr19-39440614;