Genetic Variant FBXO45:p.Ala11Ala (chr3-196569017-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001105573.2(FBXO45):c.33C>T(p.Ala11Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0036 in 1,013,250 control chromosomes in the GnomAD database, including 122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0097 ( 55 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 67 hom. )

Consequence

FBXO45
NM_001105573.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.679

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 3-196569017-C-T is Benign according to our data. Variant chr3-196569017-C-T is described in ClinVar as [Benign]. Clinvar id is 773676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.679 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXO45	NM_001105573.2 link	c.33C>T	p.Ala11Ala	synonymous_variant	Exon 1 of 3	ENST00000311630.7	NP_001099043.1	P0C2W1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXO45	ENST00000311630.7 link	c.33C>T	p.Ala11Ala	synonymous_variant	Exon 1 of 3	1	NM_001105573.2	ENSP00000310332.6		P0C2W1
FBXO45	ENST00000440469.1 link	c.-220+230C>T		intron_variant	Intron 1 of 2	2		ENSP00000389868.1		C9JLC0

Frequencies

GnomAD3 genomes

AF:

0.00964

AC:

1424

AN:

147774

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0475

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0453

Gnomad SAS

AF:

0.0640

Gnomad FIN

AF:

0.000224

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00137

Gnomad OTH

AF:

0.0108

GnomAD4 exome

AF:

0.00256

AC:

2215

AN:

865368

Hom.:

Cov.:

AF XY:

0.00263

AC XY:

1062

AN XY:

403622

show subpopulations

Gnomad4 AFR exome

AF:

0.000976

Gnomad4 AMR exome

AF:

0.0819

Gnomad4 ASJ exome

AF:

0.000172

Gnomad4 EAS exome

AF:

0.0468

Gnomad4 SAS exome

AF:

0.0510

Gnomad4 FIN exome

AF:

0.000267

Gnomad4 NFE exome

AF:

0.000835

Gnomad4 OTH exome

AF:

0.00843

GnomAD4 genome

AF:

0.00968

AC:

1432

AN:

147882

Hom.:

Cov.:

AF XY:

0.0109

AC XY:

784

AN XY:

72040

show subpopulations

Gnomad4 AFR

AF:

0.00151

Gnomad4 AMR

AF:

0.0480

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0453

Gnomad4 SAS

AF:

0.0641

Gnomad4 FIN

AF:

0.000224

Gnomad4 NFE

AF:

0.00137

Gnomad4 OTH

AF:

0.0106

Alfa

AF:

0.00572

Hom.:

Bravo

AF:

0.0127

Asia WGS

AF:

0.0340

AC:

103

AN:

3050

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.98

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