16-87334102-C-T

Position:

chr16-87334102-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000311635.12(FBXO31):c.1181G>A(p.Arg394Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00559 in 1,610,220 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. R394R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0041 ( 3 hom., cov: 34)

Exomes 𝑓: 0.0057 ( 68 hom. )

Consequence

FBXO31
ENST00000311635.12 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.08

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:

ENSG00000131152 (HGNC:):

ENSG00000131152 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034515262).

BP6

Variant 16-87334102-C-T is Benign according to our data. Variant chr16-87334102-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 376898.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-87334102-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00411 (626/152334) while in subpopulation SAS AF= 0.0255 (123/4832). AF 95% confidence interval is 0.0218. There are 3 homozygotes in gnomad4. There are 329 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXO31	NM_024735.5 linkuse as main transcript	c.1181G>A	p.Arg394Gln	missense_variant	8/9	ENST00000311635.12	NP_079011.3	Q5XUX0-1
FBXO31	NM_001282683.2 linkuse as main transcript	c.665G>A	p.Arg222Gln	missense_variant	9/10		NP_001269612.1	Q5XUX0A0A0C4DGU8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXO31	ENST00000311635.12 linkuse as main transcript	c.1181G>A	p.Arg394Gln	missense_variant	8/9	1	NM_024735.5	ENSP00000310841.4		Q5XUX0-1
ENSG00000131152	ENST00000568879.1 linkuse as main transcript	c.170G>A	p.Arg57Gln	missense_variant	1/5	4		ENSP00000454386.1		H3BMH7

Frequencies

GnomAD3 genomes

AF:

0.00413

AC:

628

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000941

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0256

Gnomad FIN

AF:

0.00640

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00501

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00650

AC:

1554

AN:

239092

Hom.:

AF XY:

0.00781

AC XY:

1023

AN XY:

131002

show subpopulations

Gnomad AFR exome

AF:

0.000618

Gnomad AMR exome

AF:

0.000995

Gnomad ASJ exome

AF:

0.00320

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0214

Gnomad FIN exome

AF:

0.00771

Gnomad NFE exome

AF:

0.00607

Gnomad OTH exome

AF:

0.00442

GnomAD4 exome

AF:

0.00574

AC:

8368

AN:

1457886

Hom.:

Cov.:

AF XY:

0.00633

AC XY:

4591

AN XY:

724950

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.00135

Gnomad4 ASJ exome

AF:

0.00269

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0213

Gnomad4 FIN exome

AF:

0.00830

Gnomad4 NFE exome

AF:

0.00504

Gnomad4 OTH exome

AF:

0.00482

GnomAD4 genome

AF:

0.00411

AC:

626

AN:

152334

Hom.:

Cov.:

AF XY:

0.00442

AC XY:

329

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.000938

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0255

Gnomad4 FIN

AF:

0.00640

Gnomad4 NFE

AF:

0.00501

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00466

Hom.:

Bravo

AF:

0.00319

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.00115

AC:

ESP6500EA

AF:

0.00410

AC:

ExAC

AF:

0.00687

AC:

826

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.00480

EpiControl

AF:

0.00510

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Feb 08, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.044

DANN

Benign

0.88

DEOGEN2

Benign

0.047

T;T

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.58

T;T

MetaRNN

Benign

0.0035

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.14

N;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.23

N;.

REVEL

Benign

0.023

Sift

Benign

0.68

T;.

Sift4G

Benign

0.63

T;T

Polyphen

0.0010

B;.

Vest4

0.15

MVP

0.33

MPC

0.95

ClinPred

0.0031

GERP RS

-8.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.020

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over