Genetic Variant NM_018994.3:c.15G>A (chr1-16315404-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_018994.3(FBXO42):c.15G>A(p.Ser5Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 1,613,610 control chromosomes in the GnomAD database, including 127,500 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.33 ( 9851 hom., cov: 31)

Exomes 𝑓: 0.39 ( 117649 hom. )

Consequence

FBXO42
NM_018994.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.73

Variant links:

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]

FBXO42 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP7

Synonymous conserved (PhyloP=-1.73 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXO42	NM_018994.3 link	c.15G>A	p.Ser5Ser	synonymous_variant	Exon 2 of 10	ENST00000375592.8	NP_061867.1	Q6P3S6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXO42	ENST00000375592.8 link	c.15G>A	p.Ser5Ser	synonymous_variant	Exon 2 of 10	1	NM_018994.3	ENSP00000364742.3		Q6P3S6
FBXO42	ENST00000478089.1 link	n.-37G>A		upstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.328

AC:

49880

AN:

151910

Hom.:

9860

Cov.:

show subpopulations

Gnomad AFR

AF:

0.109

Gnomad AMI

AF:

0.436

Gnomad AMR

AF:

0.337

Gnomad ASJ

AF:

0.366

Gnomad EAS

AF:

0.674

Gnomad SAS

AF:

0.397

Gnomad FIN

AF:

0.512

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.397

Gnomad OTH

AF:

0.337

GnomAD3 exomes

AF:

0.403

AC:

101000

AN:

250818

Hom.:

22216

AF XY:

0.406

AC XY:

55009

AN XY:

135568

show subpopulations

Gnomad AFR exome

AF:

0.106

Gnomad AMR exome

AF:

0.364

Gnomad ASJ exome

AF:

0.360

Gnomad EAS exome

AF:

0.687

Gnomad SAS exome

AF:

0.392

Gnomad FIN exome

AF:

0.510

Gnomad NFE exome

AF:

0.398

Gnomad OTH exome

AF:

0.390

GnomAD4 exome

AF:

0.392

AC:

573422

AN:

1461582

Hom.:

117649

Cov.:

AF XY:

0.393

AC XY:

285798

AN XY:

727098

show subpopulations

Gnomad4 AFR exome

AF:

0.0960

Gnomad4 AMR exome

AF:

0.359

Gnomad4 ASJ exome

AF:

0.361

Gnomad4 EAS exome

AF:

0.700

Gnomad4 SAS exome

AF:

0.392

Gnomad4 FIN exome

AF:

0.508

Gnomad4 NFE exome

AF:

0.387

Gnomad4 OTH exome

AF:

0.392

GnomAD4 genome

AF:

0.328

AC:

49866

AN:

152028

Hom.:

9851

Cov.:

AF XY:

0.336

AC XY:

24963

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.109

Gnomad4 AMR

AF:

0.336

Gnomad4 ASJ

AF:

0.366

Gnomad4 EAS

AF:

0.674

Gnomad4 SAS

AF:

0.397

Gnomad4 FIN

AF:

0.512

Gnomad4 NFE

AF:

0.397

Gnomad4 OTH

AF:

0.336

Alfa

AF:

0.380

Hom.:

22461

Bravo

AF:

0.309

Asia WGS

AF:

0.466

AC:

1617

AN:

3478

EpiCase

AF:

0.402

EpiControl

AF:

0.385

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

4.7

DANN

Benign

0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over