1-16251521-C-A

Variant names:

• chr1-16251521-C-A
• NM_018994.3:c.1303G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018994.3(FBXO42):​c.1303G>T​(p.Gly435Cys) 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. 12/21 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. G435S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FBXO42 NM_018994.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.52

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18777984).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXO42	NM_018994.3	c.1303G>T	p.Gly435Cys	missense_variant	Exon 10 of 10	ENST00000375592.8	NP_061867.1
FBXO42	XM_047422747.1	c.1303G>T	p.Gly435Cys	missense_variant	Exon 12 of 12		XP_047278703.1
FBXO42	XM_047422750.1	c.1303G>T	p.Gly435Cys	missense_variant	Exon 12 of 12		XP_047278706.1
FBXO42	XM_047422751.1	c.1303G>T	p.Gly435Cys	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.1303G>T	p.Gly435Cys	missense_variant	Exon 10 of 10	1	NM_018994.3	ENSP00000364742.3
FBXO42	ENST00000444116.1	c.457G>T	p.Gly153Cys	missense_variant	Exon 4 of 4	5		ENSP00000412416.1
FBXO42	ENST00000456164.5	c.457G>T	p.Gly153Cys	missense_variant	Exon 3 of 3	2		ENSP00000415663.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T;T;T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D;.;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;.;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.043
Sift	Uncertain	0.0060	D;D;D
Sift4G	Uncertain	0.054	T;.;.
Polyphen		0.86	P;.;.
Vest4		0.23
MutPred		0.30		Gain of sheet (P = 0.0016);.;.;
MVP		0.25
MPC		0.53
ClinPred		0.72	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.39

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: chr1-16578016; COSMIC: COSV100981649;