chr19-38942655-C-A

Variant names:

• chr19-38942655-C-A
• rs781330255
• NM_024907.7:c.790G>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 12/20 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. 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.790G>T	p.Ala264Ser	missense	Exon 6 of 6	NP_079183.4
	FBXO17	NM_148169.3		c.817G>T	p.Ala273Ser	missense	Exon 6 of 6	NP_680474.1
	FBXO17	NR_104026.2		n.1002G>T		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.790G>T	p.Ala264Ser	missense	Exon 6 of 6	ENSP00000292852.3	Q96EF6
	ENSG00000269547	ENST00000599996.1	TSL:2	c.474+28G>T		intron	N/A	ENSP00000472465.1	M0R2C6
	FBXO17	ENST00000939441.1		c.832G>T	p.Ala278Ser	missense	Exon 6 of 6	ENSP00000609500.1

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

African (AFR) AF: 0.00 AC: 0 AN: 32142

American (AMR) AF: 0.00 AC: 0 AN: 42022

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25704

East Asian (EAS) AF: 0.00 AC: 0 AN: 38026

South Asian (SAS) AF: 0.00 AC: 0 AN: 83946

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53278

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106398

Other (OTH) AF: 0.00 AC: 0 AN: 59878

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.38	N
PhyloP100		1.4
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.076
Sift	Benign	0.13	T
Sift4G	Benign	0.55	T
Polyphen		0.47	P
Vest4		0.13
MutPred		0.82		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
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs781330255; hg19: chr19-39433295; COSMIC: COSV99494343; COSMIC: COSV99494343;