dbSNP rs974414837: FBXO45:p.Ala22Gly (chr3-196569049-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001105573.2(FBXO45):c.65C>G(p.Ala22Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A22V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FBXO45
NM_001105573.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.22

Publications

1 publications found

Variant links:

Genes affected

FBXO45 (HGNC:29148): (F-box protein 45) Members of the F-box protein family, such as FBXO45, 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 (summary by Jin et al., 2004 [PubMed 15520277]).[supplied by OMIM, Jan 2011]

FBXO45 links:

WDR53 (HGNC:28786): (WD repeat domain 53) This gene encodes a protein containing WD domains. The function of this gene is unknown. [provided by RefSeq, Jul 2008]

WDR53 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07185188).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105573.2. 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
	FBXO45	NM_001105573.2	MANE Select	c.65C>G	p.Ala22Gly	missense	Exon 1 of 3	NP_001099043.1	P0C2W1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FBXO45	ENST00000311630.7	TSL:1 MANE Select	c.65C>G	p.Ala22Gly	missense	Exon 1 of 3	ENSP00000310332.6	P0C2W1
WDR53	ENST00000893402.1		c.-17+86G>C		intron	N/A	ENSP00000563461.1
FBXO45	ENST00000440469.1	TSL:2	c.-220+262C>G		intron	N/A	ENSP00000389868.1	C9JLC0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

962894

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

456656

African (AFR)

AF:

0.00

AC:

AN:

17474

American (AMR)

AF:

0.00

AC:

AN:

4380

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8708

East Asian (EAS)

AF:

0.00

AC:

AN:

13664

South Asian (SAS)

AF:

0.00

AC:

AN:

18926

European-Finnish (FIN)

AF:

0.00

AC:

AN:

16710

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2298

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

846156

Other (OTH)

AF:

0.00

AC:

AN:

34578

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.082

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.31

M_CAP

Benign

0.019

MetaRNN

Benign

0.072

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

PhyloP100

2.2

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.59

REVEL

Benign

0.040

Sift

Benign

0.83

Sift4G

Benign

0.11

Polyphen

0.0

Vest4

0.23

MutPred

0.23

Gain of catalytic residue at G23 (P = 0.3854)

MVP

0.30

MPC

1.1

ClinPred

0.16

GERP RS

0.22

PromoterAI

-0.013

Neutral

(source)

Varity_R

0.075

gMVP

0.086

Mutation Taster

=96/4

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over