17-39265438-A-T

Variant names:

• chr17-39265438-A-T
• rs1031209723
• NM_032875.3:c.949T>A

Variant summary

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

The NM_032875.3(FBXL20):​c.949T>A​(p.Leu317Ile) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FBXL20 NM_032875.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.67
• Publications: 1 publications found

Genes affected

FBXL20 (HGNC:24679): (F-box and leucine rich repeat protein 20) Members of the F-box protein family, such as FBXL20, 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]

ENSG00000293195 (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=0.38301113).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032875.3. 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
	FBXL20	NM_032875.3	MANE Select	c.949T>A	p.Leu317Ile	missense	Exon 13 of 15	NP_116264.2
	FBXL20	NM_001370208.3		c.955T>A	p.Leu319Ile	missense	Exon 13 of 15	NP_001357137.2	J3KTA1
	FBXL20	NM_001370209.3		c.859T>A	p.Leu287Ile	missense	Exon 12 of 14	NP_001357138.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXL20	ENST00000264658.11	TSL:1 MANE Select	c.949T>A	p.Leu317Ile	missense	Exon 13 of 15	ENSP00000264658.6	Q96IG2-1
	FBXL20	ENST00000394294.7	TSL:1	c.853T>A	p.Leu285Ile	missense	Exon 12 of 14	ENSP00000377832.3	Q96IG2-2
	FBXL20	ENST00000577399.5	TSL:5	c.955T>A	p.Leu319Ile	missense	Exon 13 of 15	ENSP00000462878.1	J3KTA1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

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	Uncertain	0.47
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		2.7
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.14
Sift	Benign	0.073	T
Sift4G	Benign	0.10	T
Polyphen		0.77	P
Vest4		0.70
MutPred		0.62		Loss of catalytic residue at L317 (P = 0.0029)
MVP		0.17
MPC		1.0
ClinPred		0.80	D
GERP RS		5.6
Varity_R		0.14
gMVP		0.40

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

Other links and lift over

dbSNP: rs1031209723; hg19: chr17-37421691;