Variant 1-16251413-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.35 ( 10043 hom., cov: 32)

Exomes 𝑓: 0.35 ( 92945 hom. )

Consequence

FBXO42
NM_018994.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.318

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FBXO42	NM_018994.3 linkuse as main transcript	c.1411C>G	p.Pro471Ala	missense_variant	10/10	ENST00000375592.8	NP_061867.1
FBXO42	XM_047422747.1 linkuse as main transcript	c.1411C>G	p.Pro471Ala	missense_variant	12/12		XP_047278703.1
FBXO42	XM_047422750.1 linkuse as main transcript	c.1411C>G	p.Pro471Ala	missense_variant	12/12		XP_047278706.1
FBXO42	XM_047422751.1 linkuse as main transcript	c.1411C>G	p.Pro471Ala	missense_variant	12/12		XP_047278707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
FBXO42	ENST00000375592.8 linkuse as main transcript	c.1411C>G	p.Pro471Ala	missense_variant	10/10	1	NM_018994.3	ENSP00000364742	P1
FBXO42	ENST00000444116.1 linkuse as main transcript	c.565C>G	p.Pro189Ala	missense_variant	4/4	5		ENSP00000412416
FBXO42	ENST00000456164.5 linkuse as main transcript	c.565C>G	p.Pro189Ala	missense_variant	3/3	2		ENSP00000415663

Frequencies

GnomAD3 genomes

AF:

0.354

AC:

53767

AN:

151890

Hom.:

10024

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.297

AC:

74578

AN:

250894

Hom.:

12347

AF XY:

0.293

AC XY:

39841

AN XY:

135746

show subpopulations

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 SAS exome

AF:

0.155

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.:

AF XY:

0.342

AC XY:

248964

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.428

Gnomad4 AMR exome

AF:

0.184

Gnomad4 ASJ exome

AF:

0.294

Gnomad4 EAS exome

AF:

0.164

Gnomad4 SAS exome

AF:

0.160

Gnomad4 FIN exome

AF:

0.331

Gnomad4 NFE exome

AF:

0.377

Gnomad4 OTH exome

AF:

0.331

GnomAD4 genome

AF:

0.354

AC:

53823

AN:

152008

Hom.:

10043

Cov.:

AF XY:

0.346

AC XY:

25686

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.424

Gnomad4 AMR

AF:

0.262

Gnomad4 ASJ

AF:

0.289

Gnomad4 EAS

AF:

0.185

Gnomad4 SAS

AF:

0.163

Gnomad4 FIN

AF:

0.338

Gnomad4 NFE

AF:

0.367

Gnomad4 OTH

AF:

0.329

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.043

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.84

DANN

Benign

0.46

DEOGEN2

Benign

0.015

T;T;T

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.12

T;.;T

MetaRNN

Benign

0.0017

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

N;.;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

0.080

N;N;N

REVEL

Benign

0.031

Sift

Benign

0.89

T;T;T

Sift4G

Benign

0.79

T;.;.

Polyphen

0.0

B;.;.

Vest4

0.013

MPC

0.25

ClinPred

0.00039

GERP RS

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.010

gMVP

0.11

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