rs35196193

Variant names:

• chr1-16251299-C-T
• rs35196193
• NM_018994.3:c.1525G>A

Variant summary

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

The NM_018994.3(FBXO42):​c.1525G>A​(p.Ala509Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0644 in 1,614,138 control chromosomes in the GnomAD database, including 3,637 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 0.049 (235 hom., cov: 32)
  • Exomes 𝑓: 0.066 (3402 hom.)
• Consequence: FBXO42 NM_018994.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.509
• Publications: 23 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=0.0015014708).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0671 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO42	NM_018994.3	MANE Select	c.1525G>A	p.Ala509Thr	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.1525G>A	p.Ala509Thr	missense	Exon 10 of 10	ENSP00000364742.3	Q6P3S6
	FBXO42	ENST00000868586.1		c.1525G>A	p.Ala509Thr	missense	Exon 11 of 11	ENSP00000538645.1
	FBXO42	ENST00000868587.1		c.1525G>A	p.Ala509Thr	missense	Exon 11 of 11	ENSP00000538646.1

Frequencies

GnomAD3 genomes AF: 0.0489 AC: 7435 AN: 152160 Hom.: 235 Cov.: 32

Gnomad AFR AF: 0.0197

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0409

Gnomad ASJ AF: 0.0723

Gnomad EAS AF: 0.0303

Gnomad SAS AF: 0.0709

Gnomad FIN AF: 0.0412

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0687

Gnomad OTH AF: 0.0478

GnomAD2 exomes AF: 0.0550 AC: 13824 AN: 251458 AF XY: 0.0582

Gnomad AFR exome AF: 0.0193

Gnomad AMR exome AF: 0.0227

Gnomad ASJ exome AF: 0.0687

Gnomad EAS exome AF: 0.0310

Gnomad FIN exome AF: 0.0449

Gnomad NFE exome AF: 0.0692

Gnomad OTH exome AF: 0.0572

GnomAD4 exome AF: 0.0660 AC: 96555 AN: 1461860 Hom.: 3402 Cov.: 31 AF XY: 0.0664 AC XY: 48285 AN XY: 727234

African (AFR) AF: 0.0180 AC: 602 AN: 33480

American (AMR) AF: 0.0243 AC: 1088 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0716 AC: 1872 AN: 26136

East Asian (EAS) AF: 0.0229 AC: 908 AN: 39700

South Asian (SAS) AF: 0.0739 AC: 6377 AN: 86258

European-Finnish (FIN) AF: 0.0439 AC: 2347 AN: 53420

Middle Eastern (MID) AF: 0.0348 AC: 201 AN: 5768

European-Non Finnish (NFE) AF: 0.0716 AC: 79575 AN: 1111978

Other (OTH) AF: 0.0594 AC: 3585 AN: 60396

GnomAD4 genome AF: 0.0488 AC: 7437 AN: 152278 Hom.: 235 Cov.: 32 AF XY: 0.0481 AC XY: 3581 AN XY: 74462

African (AFR) AF: 0.0197 AC: 817 AN: 41572

American (AMR) AF: 0.0408 AC: 625 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0723 AC: 251 AN: 3470

East Asian (EAS) AF: 0.0303 AC: 157 AN: 5174

South Asian (SAS) AF: 0.0715 AC: 345 AN: 4822

European-Finnish (FIN) AF: 0.0412 AC: 437 AN: 10608

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0687 AC: 4674 AN: 68006

Other (OTH) AF: 0.0473 AC: 100 AN: 2116

Alfa AF: 0.0640 Hom.: 1100

Bravo AF: 0.0466

TwinsUK AF: 0.0755 AC: 280

ALSPAC AF: 0.0675 AC: 260

ESP6500AA AF: 0.0211 AC: 93

ESP6500EA AF: 0.0679 AC: 584

ExAC AF: 0.0557 AC: 6759

Asia WGS AF: 0.0520 AC: 180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.50
DANN	Benign	0.79
DEOGEN2	Benign	0.018	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.59	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.51
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.016
Sift	Benign	0.15	T
Sift4G	Benign	0.58	T
Polyphen		0.0	B
Vest4		0.011
MPC		0.25
ClinPred		0.000013	T
GERP RS		-5.0
Varity_R		0.020
gMVP		0.17
Mutation Taster		=100/0	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: rs35196193; hg19: chr1-16577794;