NM_024735.5:c.1339G>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_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

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive non-syndromic intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
cerebral palsy
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
intellectual disability, autosomal recessive
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
intellectual disability, autosomal recessive 45
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

FBXO31 links:

ENSG00000131152 (HGNC:):

ENSG00000131152 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.057759494).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024735.5. 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
	FBXO31	NM_024735.5	MANE Select	c.1339G>A	p.Val447Met	missense	Exon 8 of 9	NP_079011.3
	FBXO31	NM_001282683.2		c.823G>A	p.Val275Met	missense	Exon 9 of 10	NP_001269612.1	A0A0C4DGU8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FBXO31	ENST00000311635.12	TSL:1 MANE Select	c.1339G>A	p.Val447Met	missense	Exon 8 of 9	ENSP00000310841.4	Q5XUX0-1
ENSG00000131152	ENST00000568879.1	TSL:4	c.328G>A	p.Val110Met	missense	Exon 1 of 5	ENSP00000454386.1	H3BMH7
FBXO31	ENST00000636077.2	TSL:5	c.1426G>A	p.Val476Met	missense	Exon 9 of 10	ENSP00000490402.2	A0A1B0GV77

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

GnomAD2 exomes

AF:

0.000184

AC:

AN:

244738

AF XY:

0.000112

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 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

African (AFR)

AF:

0.0000598

AC:

AN:

33464

American (AMR)

AF:

0.000247

AC:

AN:

44624

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26048

East Asian (EAS)

AF:

0.000428

AC:

AN:

39690

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86134

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52358

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

1111512

Other (OTH)

AF:

0.0000166

AC:

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000105

AC:

AN:

152342

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.0000721

AC:

AN:

41592

American (AMR)

AF:

0.000131

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00135

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000894

Hom.:

Bravo

AF:

0.000110

ExAC

AF:

0.000149

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.074

MetaRNN

Benign

0.058

MetaSVM

Uncertain

-0.16

MutationAssessor

Pathogenic

3.1

PhyloP100

4.0

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.95

REVEL

Benign

0.20

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.051

Polyphen

1.0

Vest4

0.45

MVP

0.64

MPC

1.9

ClinPred

0.18

GERP RS

5.3

PromoterAI

-0.00040

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.43

gMVP

0.78

Mutation Taster

=47/53

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over