1-16251340-A-T

Variant names:

• chr1-16251340-A-T
• NM_018994.3:c.1484T>A

Variant summary

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

The NM_018994.3(FBXO42):​c.1484T>A​(p.Leu495Gln) variant causes a missense change. 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: FBXO42 NM_018994.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.04
• Publications: 0 publications found

Genes affected

FBXO42 (HGNC:29249): (F-box protein 42) Members of the F-box protein family, such as FBXO42, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (SKP1A; 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, Dec 2010]

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=0.34621733).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXO42	NM_018994.3	c.1484T>A	p.Leu495Gln	missense_variant	Exon 10 of 10	ENST00000375592.8	NP_061867.1
FBXO42	XM_047422747.1	c.1484T>A	p.Leu495Gln	missense_variant	Exon 12 of 12		XP_047278703.1
FBXO42	XM_047422750.1	c.1484T>A	p.Leu495Gln	missense_variant	Exon 12 of 12		XP_047278706.1
FBXO42	XM_047422751.1	c.1484T>A	p.Leu495Gln	missense_variant	Exon 12 of 12		XP_047278707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXO42	ENST00000375592.8	c.1484T>A	p.Leu495Gln	missense_variant	Exon 10 of 10	1	NM_018994.3	ENSP00000364742.3
FBXO42	ENST00000444116.1	c.638T>A	p.Leu213Gln	missense_variant	Exon 4 of 4	5		ENSP00000412416.1
FBXO42	ENST00000456164.5	c.638T>A	p.Leu213Gln	missense_variant	Exon 3 of 3	2		ENSP00000415663.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1484T>A (p.L495Q) alteration is located in exon 10 (coding exon 9) of the FBXO42 gene. This alteration results from a T to A substitution at nucleotide position 1484, causing the leucine (L) at amino acid position 495 to be replaced by a glutamine (Q). 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	Benign	0.11
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T;T;T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;.;D
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.35	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.90	L;.;.
PhyloP100		5.0
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.50	N;N;N
REVEL	Benign	0.24
Sift	Benign	0.033	D;D;D
Sift4G	Benign	0.65	T;.;.
Polyphen		0.99	D;.;.
Vest4		0.43
MutPred		0.35		Loss of catalytic residue at L495 (P = 0.0035);.;.;
MVP		0.73
MPC		0.91
ClinPred		0.69	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.54
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

hg19: chr1-16577835;