Genetic Variant FBXO30:p.Val375Met (chr6-145805283-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032145.5(FBXO30):c.1123G>A(p.Val375Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 1,613,724 control chromosomes in the GnomAD database, including 132,955 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.36 ( 10369 hom., cov: 33)

Exomes 𝑓: 0.41 ( 122586 hom. )

Consequence

FBXO30
NM_032145.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.231

Variant links:

Genes affected

FBXO30 (HGNC:15600): (F-box protein 30) This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of the ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbxs class and it is upregulated in nasopharyngeal carcinoma. [provided by RefSeq, Jul 2008]

FBXO30 links:

EPM2A-DT (HGNC:48990): (EPM2A divergent transcript)

EPM2A-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.1279214E-4).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXO30	NM_032145.5 link	c.1123G>A	p.Val375Met	missense_variant	Exon 2 of 3	ENST00000237281.5	NP_115521.3
FBXO30	NM_001348092.2 link	c.1123G>A	p.Val375Met	missense_variant	Exon 2 of 3		NP_001335021.1	Q8TB52
FBXO30	XM_047419398.1 link	c.1231G>A	p.Val411Met	missense_variant	Exon 2 of 3		XP_047275354.1
EPM2A-DT	NR_038246.1 link	n.53-23078C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXO30	ENST00000237281.5 link	c.1123G>A	p.Val375Met	missense_variant	Exon 2 of 3	1	NM_032145.5	ENSP00000237281.3		Q8TB52
EPM2A-DT	ENST00000629681.1 link	n.91-4495C>T		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.358

AC:

54383

AN:

151974

Hom.:

10356

Cov.:

show subpopulations

Gnomad AFR

AF:

0.248

Gnomad AMI

AF:

0.456

Gnomad AMR

AF:

0.286

Gnomad ASJ

AF:

0.385

Gnomad EAS

AF:

0.258

Gnomad SAS

AF:

0.479

Gnomad FIN

AF:

0.493

Gnomad MID

AF:

0.420

Gnomad NFE

AF:

0.416

Gnomad OTH

AF:

0.352

GnomAD3 exomes

AF:

0.380

AC:

95461

AN:

251026

Hom.:

19610

AF XY:

0.396

AC XY:

53755

AN XY:

135654

show subpopulations

Gnomad AFR exome

AF:

0.249

Gnomad AMR exome

AF:

0.212

Gnomad ASJ exome

AF:

0.381

Gnomad EAS exome

AF:

0.246

Gnomad SAS exome

AF:

0.488

Gnomad FIN exome

AF:

0.488

Gnomad NFE exome

AF:

0.422

Gnomad OTH exome

AF:

0.388

GnomAD4 exome

AF:

0.405

AC:

592142

AN:

1461630

Hom.:

122586

Cov.:

AF XY:

0.409

AC XY:

297535

AN XY:

727112

show subpopulations

Gnomad4 AFR exome

AF:

0.249

Gnomad4 AMR exome

AF:

0.221

Gnomad4 ASJ exome

AF:

0.387

Gnomad4 EAS exome

AF:

0.265

Gnomad4 SAS exome

AF:

0.481

Gnomad4 FIN exome

AF:

0.481

Gnomad4 NFE exome

AF:

0.414

Gnomad4 OTH exome

AF:

0.396

GnomAD4 genome

AF:

0.358

AC:

54414

AN:

152094

Hom.:

10369

Cov.:

AF XY:

0.361

AC XY:

26854

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.248

Gnomad4 AMR

AF:

0.285

Gnomad4 ASJ

AF:

0.385

Gnomad4 EAS

AF:

0.258

Gnomad4 SAS

AF:

0.478

Gnomad4 FIN

AF:

0.493

Gnomad4 NFE

AF:

0.416

Gnomad4 OTH

AF:

0.358

Alfa

AF:

0.395

Hom.:

27185

Bravo

AF:

0.335

TwinsUK

AF:

0.422

AC:

1565

ALSPAC

AF:

0.416

AC:

1604

ESP6500AA

AF:

0.254

AC:

1117

ESP6500EA

AF:

0.413

AC:

3553

ExAC

AF:

0.390

AC:

47294

Asia WGS

AF:

0.394

AC:

1369

AN:

3478

EpiCase

AF:

0.417

EpiControl

AF:

0.423

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

CADD

Benign

9.3

DANN

Benign

0.71

DEOGEN2

Benign

0.015

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.16

MetaRNN

Benign

0.00011

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.69

PrimateAI

Benign

0.29

PROVEAN

Benign

0.11

REVEL

Benign

0.082

Sift

Benign

0.056

Sift4G

Benign

0.13

Polyphen

0.043

Vest4

0.14

MPC

0.23

ClinPred

0.0016

GERP RS

-3.2

Varity_R

0.039

gMVP

0.15

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