Variant 1-224114143-C-G 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_015176.4(FBXO28):c.14C>G(p.Ala5Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000288 in 1,389,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A5K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

FBXO28
NM_015176.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.56

Variant links:

Genes affected

FBXO28 (HGNC:29046): (F-box protein 28) Members of the F-box protein family, such as FBXO28, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (MIM 601434), cullin (see CUL1; MIM 603134), and F-box proteins, act as protein-ubiquitin ligases. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains (Jin et al., 2004 [PubMed 15520277]).[supplied by OMIM, Mar 2008]

FBXO28 links:

FBXO28 (HGNC:):

FBXO28 links:

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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=0.043448776).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXO28	NM_015176.4 linkuse as main transcript	c.14C>G	p.Ala5Gly	missense_variant	1/5	ENST00000366862.10	NP_055991.1	Q9NVF7-1
FBXO28	NM_001136115.3 linkuse as main transcript	c.14C>G	p.Ala5Gly	missense_variant	1/4		NP_001129587.1	Q9NVF7-2
FBXO28	NR_049764.2 linkuse as main transcript	n.33C>G		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FBXO28	ENST00000366862.10 linkuse as main transcript	c.14C>G	p.Ala5Gly	missense_variant	1/5	1	NM_015176.4	ENSP00000355827.5	Q9NVF7-1
FBXO28	ENST00000424254.6 linkuse as main transcript	c.14C>G	p.Ala5Gly	missense_variant	1/4	1		ENSP00000416888.2	Q9NVF7-2
FBXO28	ENST00000523990.1 linkuse as main transcript	n.14C>G		non_coding_transcript_exon_variant	1/4	2		ENSP00000430632.1	B4E0H5
FBXO28	ENST00000483773.1 linkuse as main transcript	n.-28C>G		upstream_gene_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000288

AC:

AN:

1389524

Hom.:

Cov.:

AF XY:

0.00000292

AC XY:

AN XY:

684488

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000186

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

FBXO28: PM2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.033

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.018

T;.

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.35

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.043

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.55

N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.36

N;N

REVEL

Benign

0.14

Sift

Benign

0.42

T;T

Sift4G

Benign

0.59

T;T

Polyphen

0.0020

B;.

Vest4

0.18

MutPred

0.23

Gain of loop (P = 0.0079);Gain of loop (P = 0.0079);

MVP

0.10

MPC

0.72

ClinPred

0.31

GERP RS

4.6

Varity_R

0.16

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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