NM_001371389.2:c.2186G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001371389.2(FBXO41):​c.2186G>C​(p.Arg729Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. R729H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

FBXO41
NM_001371389.2 missense

Scores

8
6
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.24
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.799

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FBXO41NM_001371389.2 linkc.2186G>C p.Arg729Pro missense_variant Exon 10 of 13 ENST00000520530.3 NP_001358318.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FBXO41ENST00000520530.3 linkc.2186G>C p.Arg729Pro missense_variant Exon 10 of 13 5 NM_001371389.2 ENSP00000430968.2 Q8TF61
FBXO41ENST00000295133.9 linkc.2186G>C p.Arg729Pro missense_variant Exon 9 of 12 1 ENSP00000295133.6 Q8TF61
FBXO41ENST00000521871.5 linkc.2186G>C p.Arg729Pro missense_variant Exon 10 of 13 5 ENSP00000428646.1 Q8TF61

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.40
D
BayesDel_noAF
Pathogenic
0.34
CADD
Pathogenic
33
DANN
Uncertain
1.0
DEOGEN2
Benign
0.018
T;T;T
Eigen
Pathogenic
0.70
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.95
D;.;.
M_CAP
Benign
0.045
D
MetaRNN
Pathogenic
0.80
D;D;D
MetaSVM
Benign
-0.30
T
MutationAssessor
Benign
1.7
L;L;L
PrimateAI
Pathogenic
0.85
D
PROVEAN
Uncertain
-2.8
.;D;.
REVEL
Uncertain
0.32
Sift
Uncertain
0.0040
.;D;.
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
D;D;D
Vest4
0.91
MutPred
0.58
Loss of MoRF binding (P = 0.0023);Loss of MoRF binding (P = 0.0023);Loss of MoRF binding (P = 0.0023);
MVP
0.57
MPC
1.0
ClinPred
0.99
D
GERP RS
4.8
Varity_R
0.75
gMVP
0.83

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-73487972; API