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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018994.3(FBXO42):c.1411C>A(p.Pro471Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,966 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P471A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Failed GnomAD Quality Control

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.021453321).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FBXO42	NM_018994.3 linkuse as main transcript	c.1411C>A	p.Pro471Thr	missense_variant	10/10	ENST00000375592.8	NP_061867.1
FBXO42	XM_047422747.1 linkuse as main transcript	c.1411C>A	p.Pro471Thr	missense_variant	12/12		XP_047278703.1
FBXO42	XM_047422750.1 linkuse as main transcript	c.1411C>A	p.Pro471Thr	missense_variant	12/12		XP_047278706.1
FBXO42	XM_047422751.1 linkuse as main transcript	c.1411C>A	p.Pro471Thr	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>A	p.Pro471Thr	missense_variant	10/10	1	NM_018994.3	ENSP00000364742	P1
FBXO42	ENST00000444116.1 linkuse as main transcript	c.565C>A	p.Pro189Thr	missense_variant	4/4	5		ENSP00000412416
FBXO42	ENST00000456164.5 linkuse as main transcript	c.565C>A	p.Pro189Thr	missense_variant	3/3	2		ENSP00000415663

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151966

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250894

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135746

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000137

AC:

AN:

1461866

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151966

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74224

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

5.6

DANN

Benign

0.19

DEOGEN2

Benign

0.016

T;T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.18

T;.;T

M_CAP

Benign

0.0061

MetaRNN

Benign

0.021

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

0.25

N;N;N

REVEL

Benign

0.044

Sift

Benign

0.77

T;T;T

Sift4G

Benign

0.91

T;.;.

Polyphen

0.0

B;.;.

Vest4

0.014

MutPred

0.092

Gain of sheet (P = 0.0344);.;.;

MVP

0.15

MPC

0.28

ClinPred

0.023

GERP RS

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.022

gMVP

0.17

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