dbSNP rs748830200: FBXO41:p.Glu482* (chr2-73265402-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001371389.2(FBXO41):c.1444G>T(p.Glu482*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000686 in 1,458,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

FBXO41
NM_001371389.2 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.17

Publications

1 publications found

Variant links:

Genes affected

FBXO41 (HGNC:29409): (F-box protein 41) This gene encodes a member of the F-box protein family, which is characterized by an approximately 40 amino acid motif, the F-box. F-box proteins constitute one of the four subunits of the SCF ubiquitin protein ligase complex that plays a role in phosphorylation-dependent ubiquitination. F-box proteins are divided into three classes depending on the interaction substrate domain each contains in addition to the F-box motif: FBXW proteins contain WD-40 domains, FBXL proteins contain leucine-rich repeats, and FBXO proteins contain either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the FBXO class. [provided by RefSeq, Feb 2014]

FBXO41 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXO41	NM_001371389.2 link	c.1444G>T	p.Glu482*	stop_gained	Exon 5 of 13	ENST00000520530.3	NP_001358318.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
FBXO41	ENST00000520530.3 link	c.1444G>T	p.Glu482*	stop_gained	Exon 5 of 13	5	NM_001371389.2	ENSP00000430968.2
FBXO41	ENST00000295133.9 link	c.1444G>T	p.Glu482*	stop_gained	Exon 4 of 12	1		ENSP00000295133.6
FBXO41	ENST00000521871.5 link	c.1444G>T	p.Glu482*	stop_gained	Exon 5 of 13	5		ENSP00000428646.1
FBXO41	ENST00000519873.1 link	n.*81G>T		downstream_gene_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000409

AC:

AN:

244694

AF XY:

0.00000749

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458594

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725824

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.0000224

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26112

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50542

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111716

Other (OTH)

AF:

0.00

AC:

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.56

BayesDel_noAF

Pathogenic

0.65

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0

.;.;.

Eigen

Pathogenic

1.1

Eigen_PC

Pathogenic

0.96

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.0

.;.;.

MetaRNN

Benign

0.0

.;.;.

MutationAssessor

Benign

0.0

.;.;.

PhyloP100

7.2

PROVEAN

Benign

0.0

.;.;.

REVEL

Benign

0.0

Sift

Pathogenic

0.0

.;.;.

Sift4G

Pathogenic

0.0

.;.;.

Vest4

0.26

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=9/191

disease causing (fs/PTC)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.58

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.58

Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over