chr2-73263977-C-T

Variant summary

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

The NM_001371389.2(FBXO41):​c.1883G>A​(p.Gly628Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000268 in 1,454,506 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G628V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

FBXO41
NM_001371389.2 missense

Scores

5
8
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.69
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, 0.793

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FBXO41NM_001371389.2 linkc.1883G>A p.Gly628Glu missense_variant Exon 7 of 13 ENST00000520530.3 NP_001358318.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FBXO41ENST00000520530.3 linkc.1883G>A p.Gly628Glu missense_variant Exon 7 of 13 5 NM_001371389.2 ENSP00000430968.2 Q8TF61
FBXO41ENST00000295133.9 linkc.1883G>A p.Gly628Glu missense_variant Exon 6 of 12 1 ENSP00000295133.6 Q8TF61
FBXO41ENST00000521871.5 linkc.1883G>A p.Gly628Glu missense_variant Exon 7 of 13 5 ENSP00000428646.1 Q8TF61

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000428
AC:
1
AN:
233916
Hom.:
0
AF XY:
0.00000787
AC XY:
1
AN XY:
127002
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000951
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000268
AC:
39
AN:
1454506
Hom.:
0
Cov.:
33
AF XY:
0.0000249
AC XY:
18
AN XY:
722888
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000343
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000828
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.87
BayesDel_addAF
Pathogenic
0.21
D
BayesDel_noAF
Uncertain
0.060
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.28
T;T;T
Eigen
Uncertain
0.51
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.89
D;.;.
M_CAP
Benign
0.014
T
MetaRNN
Pathogenic
0.79
D;D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.6
L;L;L
PrimateAI
Pathogenic
0.90
D
PROVEAN
Uncertain
-2.7
.;D;.
REVEL
Uncertain
0.31
Sift
Benign
0.064
.;T;.
Sift4G
Uncertain
0.037
D;D;D
Polyphen
1.0
D;D;D
Vest4
0.95
MutPred
0.36
Loss of MoRF binding (P = 0.0179);Loss of MoRF binding (P = 0.0179);Loss of MoRF binding (P = 0.0179);
MVP
0.35
MPC
1.2
ClinPred
0.93
D
GERP RS
5.1
Varity_R
0.53
gMVP
0.69

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.

Other links and lift over

dbSNP: rs778503960; hg19: chr2-73491105; API