5-108020997-C-T

Position:

• chr5-108020997-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001163315.3(FBXL17):​c.1750G>A​(p.Val584Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FBXL17 NM_001163315.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.78

Genes affected

FBXL17 (HGNC:13615): (F-box and leucine rich repeat protein 17) Members of the F-box protein family, such as FBXL17, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (MIM 601434), cullin (see CUL1; MIM 603134), and F-box proteins, act as protein-ubiquitin ligases. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains (Jin et al., 2004 [PubMed 15520277]).[supplied by OMIM, Mar 2008]

FBXL17 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXL17	NM_001163315.3	c.1750G>A	p.Val584Met	missense_variant	7/9	ENST00000542267.7	NP_001156787.2
FBXL17	XM_005272048.5	c.1750G>A	p.Val584Met	missense_variant	7/8		XP_005272105.1
FBXL17	XM_011543574.4	c.1750G>A	p.Val584Met	missense_variant	7/8		XP_011541876.1
FBXL17	XM_011543575.3	c.1750G>A	p.Val584Met	missense_variant	7/8		XP_011541877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXL17	ENST00000542267.7	c.1750G>A	p.Val584Met	missense_variant	7/9	1	NM_001163315.3	ENSP00000437464.2
FBXL17	ENST00000496714.2	c.757G>A	p.Val253Met	missense_variant	6/7	1		ENSP00000418111.2
FBXL17	ENST00000481160.1	n.406G>A		non_coding_transcript_exon_variant	5/5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 19, 2022

The c.1750G>A (p.V584M) alteration is located in exon 7 (coding exon 7) of the FBXL17 gene. This alteration results from a G to A substitution at nucleotide position 1750, causing the valine (V) at amino acid position 584 to be replaced by a methionine (M). 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	0.94
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	.;T;.;.
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	D;D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.66	D;D;D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.8	.;L;.;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.7	N;N;.;N
REVEL	Benign	0.28
Sift	Uncertain	0.019	D;D;.;D
Sift4G	Uncertain	0.012	D;D;D;D
Polyphen		1.0, 1.0	.;D;.;D
Vest4		0.77
MutPred		0.31		.;Gain of catalytic residue at V584 (P = 0.0327);.;.;
MVP		0.41
MPC		1.6
ClinPred		0.96	D
GERP RS		5.5
Varity_R		0.43
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr5-107356698;