Variant 16-87333944-C-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_024735.5(FBXO31):c.1339G>A(p.Val447Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000912 in 1,612,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000090 ( 0 hom. )

Consequence

FBXO31
NM_024735.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.98

Variant links:

Genes affected

FBXO31 (HGNC:16510): (F-box protein 31) This gene is a member of the F-box family. Members are classified into three classes according to the substrate interaction domain, FBW for WD40 repeats, FBL for leucing-rich repeats, and FBXO for other domains. This protein, classified into the last category because of the lack of a recognizable substrate binding domain, has been proposed to be a component of the SCF ubiquitination complex. It is thought to bind and recruit substrate for ubiquitination and degradation. This protein may have a role in regulating the cell cycle as well as dendrite growth and neuronal migration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

FBXO31 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=0.057759494).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBXO31	NM_024735.5 linkuse as main transcript	c.1339G>A	p.Val447Met	missense_variant	8/9	ENST00000311635.12
FBXO31	NM_001282683.2 linkuse as main transcript	c.823G>A	p.Val275Met	missense_variant	9/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBXO31	ENST00000311635.12 linkuse as main transcript	c.1339G>A	p.Val447Met	missense_variant	8/9	1	NM_024735.5	P1	Q5XUX0-1
FBXO31	ENST00000636077.2 linkuse as main transcript	c.1426G>A	p.Val476Met	missense_variant	9/10	5
FBXO31	ENST00000618298.6 linkuse as main transcript	c.823G>A	p.Val275Met	missense_variant	8/9	5
FBXO31	ENST00000565593.1 linkuse as main transcript	c.*45G>A		3_prime_UTR_variant, NMD_transcript_variant	2/3	5

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000184

AC:

AN:

244738

Hom.:

AF XY:

0.000112

AC XY:

AN XY:

133398

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.000262

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00134

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000916

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000897

AC:

131

AN:

1459936

Hom.:

Cov.:

AF XY:

0.0000799

AC XY:

AN XY:

726238

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000247

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000428

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000882

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000105

AC:

AN:

152342

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0000721

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000894

Hom.:

Bravo

AF:

0.000110

ExAC

AF:

0.000149

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 16, 2023

The c.1339G>A (p.V447M) alteration is located in exon 8 (coding exon 8) of the FBXO31 gene. This alteration results from a G to A substitution at nucleotide position 1339, causing the valine (V) at amino acid position 447 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

T;T

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.97

D;D

M_CAP

Benign

0.074

MetaRNN

Benign

0.058

T;T

MetaSVM

Uncertain

-0.16

MutationAssessor

Pathogenic

3.1

M;.

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.95

N;.

REVEL

Benign

0.20

Sift

Uncertain

0.0060

D;.

Sift4G

Uncertain

0.051

T;T

Polyphen

1.0

D;.

Vest4

0.45

MVP

0.64

MPC

1.9

ClinPred

0.18

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.43

gMVP

0.78

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over