chr1-16251221-T-C

Variant names:

• chr1-16251221-T-C
• rs1057483349
• NM_018994.3:c.1603A>G

Variant summary

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

The NM_018994.3(FBXO42):​c.1603A>G​(p.Asn535Asp) 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: 6.87
• 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=0.28784913).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018994.3. 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
	FBXO42	NM_018994.3	MANE Select	c.1603A>G	p.Asn535Asp	missense	Exon 10 of 10	NP_061867.1	Q6P3S6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO42	ENST00000375592.8	TSL:1 MANE Select	c.1603A>G	p.Asn535Asp	missense	Exon 10 of 10	ENSP00000364742.3	Q6P3S6
	FBXO42	ENST00000868586.1		c.1603A>G	p.Asn535Asp	missense	Exon 11 of 11	ENSP00000538645.1
	FBXO42	ENST00000868587.1		c.1603A>G	p.Asn535Asp	missense	Exon 11 of 11	ENSP00000538646.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251280 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.43
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.90	L
PhyloP100		6.9
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.11
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.14	T
Polyphen		0.99	D
Vest4		0.45
MutPred		0.24		Gain of sheet (P = 0.0221)
MVP		0.68
MPC		0.96
ClinPred		0.76	D
GERP RS		5.5
Varity_R		0.34
gMVP		0.42
Mutation Taster		=68/32	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

dbSNP: rs1057483349; hg19: chr1-16577716;