1-16251413-G-C

Variant names:

• chr1-16251413-G-C
• rs12069239
• NM_018994.3:c.1411C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018994.3(FBXO42):​c.1411C>G​(p.Pro471Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 1,613,826 control chromosomes in the GnomAD database, including 102,988 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.35 (10043 hom., cov: 32)
  • Exomes 𝑓: 0.35 (92945 hom.)
• Consequence: FBXO42 NM_018994.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.318
• Publications: 37 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001695782).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO42	NM_018994.3	MANE Select	c.1411C>G	p.Pro471Ala	missense	Exon 10 of 10	NP_061867.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO42	ENST00000375592.8	TSL:1 MANE Select	c.1411C>G	p.Pro471Ala	missense	Exon 10 of 10	ENSP00000364742.3
	FBXO42	ENST00000868586.1		c.1411C>G	p.Pro471Ala	missense	Exon 11 of 11	ENSP00000538645.1
	FBXO42	ENST00000868587.1		c.1411C>G	p.Pro471Ala	missense	Exon 11 of 11	ENSP00000538646.1

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53767 AN: 151890 Hom.: 10024 Cov.: 32

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.333

GnomAD2 exomes AF: 0.297 AC: 74578 AN: 250894 AF XY: 0.293

Gnomad AFR exome AF: 0.434

Gnomad AMR exome AF: 0.176

Gnomad ASJ exome AF: 0.292

Gnomad EAS exome AF: 0.184

Gnomad FIN exome AF: 0.338

Gnomad NFE exome AF: 0.363

Gnomad OTH exome AF: 0.316

GnomAD4 exome AF: 0.348 AC: 509312 AN: 1461818 Hom.: 92945 Cov.: 57 AF XY: 0.342 AC XY: 248964 AN XY: 727206

African (AFR) AF: 0.428 AC: 14333 AN: 33478

American (AMR) AF: 0.184 AC: 8218 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 7685 AN: 26134

East Asian (EAS) AF: 0.164 AC: 6508 AN: 39700

South Asian (SAS) AF: 0.160 AC: 13838 AN: 86254

European-Finnish (FIN) AF: 0.331 AC: 17657 AN: 53418

Middle Eastern (MID) AF: 0.240 AC: 1387 AN: 5768

European-Non Finnish (NFE) AF: 0.377 AC: 419712 AN: 1111952

Other (OTH) AF: 0.331 AC: 19974 AN: 60390

GnomAD4 genome AF: 0.354 AC: 53823 AN: 152008 Hom.: 10043 Cov.: 32 AF XY: 0.346 AC XY: 25686 AN XY: 74314

African (AFR) AF: 0.424 AC: 17578 AN: 41462

American (AMR) AF: 0.262 AC: 3999 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1004 AN: 3470

East Asian (EAS) AF: 0.185 AC: 957 AN: 5160

South Asian (SAS) AF: 0.163 AC: 788 AN: 4832

European-Finnish (FIN) AF: 0.338 AC: 3573 AN: 10580

Middle Eastern (MID) AF: 0.247 AC: 72 AN: 292

European-Non Finnish (NFE) AF: 0.367 AC: 24907 AN: 67928

Other (OTH) AF: 0.329 AC: 694 AN: 2112

Alfa AF: 0.331 Hom.: 5159

Bravo AF: 0.354

TwinsUK AF: 0.390 AC: 1446

ALSPAC AF: 0.375 AC: 1445

ESP6500AA AF: 0.423 AC: 1864

ESP6500EA AF: 0.359 AC: 3084

ExAC AF: 0.303 AC: 36844

Asia WGS AF: 0.191 AC: 667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.043
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.84
DANN	Benign	0.46
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.12	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.32
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.080	N
REVEL	Benign	0.031
Sift	Benign	0.89	T
Sift4G	Benign	0.79	T
Polyphen		0.0	B
Vest4		0.013
MPC		0.25
ClinPred		0.00039	T
GERP RS		0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.010
gMVP		0.11
Mutation Taster		=99/1	polymorphism (auto)

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: rs12069239; hg19: chr1-16577908; COSMIC: COSV65044788;