Variant 16-87335295-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_024735.5(FBXO31):c.996+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000123 in 1,612,818 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00073 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

FBXO31
NM_024735.5 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.28

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 16-87335295-G-A is Benign according to our data. Variant chr16-87335295-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3053211.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBXO31	NM_024735.5 linkuse as main transcript	c.996+9C>T		intron_variant		ENST00000311635.12
FBXO31	NM_001282683.2 linkuse as main transcript	c.480+9C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
FBXO31	ENST00000311635.12 linkuse as main transcript	c.996+9C>T	intron_variant	1	NM_024735.5	P1	Q5XUX0-1
FBXO31	ENST00000618298.6 linkuse as main transcript	c.480+9C>T	intron_variant	5
FBXO31	ENST00000636077.2 linkuse as main transcript	c.1083+9C>T	intron_variant	5
FBXO31	ENST00000565593.1 linkuse as main transcript	c.288-1174C>T	intron_variant, NMD_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.000729

AC:

111

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000224

AC:

AN:

249700

Hom.:

AF XY:

0.000222

AC XY:

AN XY:

135166

show subpopulations

Gnomad AFR exome

AF:

0.00303

Gnomad AMR exome

AF:

0.000116

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:

0.0000177

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000603

AC:

AN:

1460514

Hom.:

Cov.:

AF XY:

0.0000482

AC XY:

AN XY:

726594

show subpopulations

Gnomad4 AFR exome

AF:

0.00206

Gnomad4 AMR exome

AF:

0.000112

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:

0.00000450

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000729

AC:

111

AN:

152304

Hom.:

Cov.:

AF XY:

0.000658

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00241

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000453

Hom.:

Bravo

AF:

0.000858

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

FBXO31-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 26, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

Cadd

Benign

0.0050

Dann

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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