Genetic Variant FBXO41:p.Leu794Pro (chr2-73260457-A-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001371389.2(FBXO41):c.2381T>C(p.Leu794Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FBXO41
NM_001371389.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.87

Publications

0 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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.887

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371389.2. 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
	FBXO41	NM_001371389.2	MANE Select	c.2381T>C	p.Leu794Pro	missense	Exon 11 of 13	NP_001358318.1	Q8TF61
	FBXO41	NM_001080410.4		c.2381T>C	p.Leu794Pro	missense	Exon 15 of 17	NP_001073879.2	Q8TF61

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FBXO41	ENST00000520530.3	TSL:5 MANE Select	c.2381T>C	p.Leu794Pro	missense	Exon 11 of 13	ENSP00000430968.2	Q8TF61
FBXO41	ENST00000295133.9	TSL:1	c.2381T>C	p.Leu794Pro	missense	Exon 10 of 12	ENSP00000295133.6	Q8TF61
FBXO41	ENST00000521871.5	TSL:5	c.2381T>C	p.Leu794Pro	missense	Exon 11 of 13	ENSP00000428646.1	Q8TF61

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1456096

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723672

African (AFR)

AF:

0.00

AC:

AN:

33370

American (AMR)

AF:

0.00

AC:

AN:

44096

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25980

East Asian (EAS)

AF:

0.00

AC:

AN:

39450

South Asian (SAS)

AF:

0.00

AC:

AN:

84676

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53076

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109532

Other (OTH)

AF:

0.00

AC:

AN:

60158

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.20

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.11

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.85

M_CAP

Benign

0.077

MetaRNN

Pathogenic

0.89

MetaSVM

Benign

-0.52

MutationAssessor

Benign

1.7

PhyloP100

6.9

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-2.9

REVEL

Uncertain

0.61

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.94

MutPred

0.76

Loss of stability (P = 0.0316)

MVP

0.80

MPC

1.3

ClinPred

0.99

GERP RS

4.9

Varity_R

0.77

gMVP

0.86

Mutation Taster

=34/66

disease causing

(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