17-38951613-C-A

Variant summary

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

The NM_001008777.3(FBXO47):​c.584G>T​(p.Arg195Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,444 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000041 ( 0 hom. )

Consequence

FBXO47
NM_001008777.3 missense

Scores

3
10
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.29
Variant links:
Genes affected
FBXO47 (HGNC:31969): (F-box protein 47)

Genome browser will be placed here

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, 0.775

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FBXO47NM_001008777.3 linkuse as main transcriptc.584G>T p.Arg195Leu missense_variant 6/11 ENST00000378079.3 NP_001008777.2
FBXO47XM_011524865.3 linkuse as main transcriptc.506G>T p.Arg169Leu missense_variant 6/11 XP_011523167.1
FBXO47XM_011524866.4 linkuse as main transcriptc.413G>T p.Arg138Leu missense_variant 5/10 XP_011523168.1
FBXO47XM_011524867.3 linkuse as main transcriptc.584G>T p.Arg195Leu missense_variant 6/10 XP_011523169.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FBXO47ENST00000378079.3 linkuse as main transcriptc.584G>T p.Arg195Leu missense_variant 6/111 NM_001008777.3 ENSP00000367319 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251272
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135820
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:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000411
AC:
6
AN:
1461444
Hom.:
0
Cov.:
30
AF XY:
0.00000413
AC XY:
3
AN XY:
727048
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:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 17, 2024The c.584G>T (p.R195L) alteration is located in exon 6 (coding exon 5) of the FBXO47 gene. This alteration results from a G to T substitution at nucleotide position 584, causing the arginine (R) at amino acid position 195 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.26
BayesDel_addAF
Pathogenic
0.23
D
BayesDel_noAF
Pathogenic
0.19
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.11
T
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.63
T
M_CAP
Benign
0.063
D
MetaRNN
Pathogenic
0.78
D
MetaSVM
Uncertain
0.050
D
MutationAssessor
Uncertain
2.5
M
MutationTaster
Benign
1.0
D
PrimateAI
Benign
0.48
T
PROVEAN
Uncertain
-4.0
D
REVEL
Uncertain
0.45
Sift
Uncertain
0.010
D
Sift4G
Uncertain
0.017
D
Polyphen
1.0
D
Vest4
0.80
MutPred
0.39
Gain of ubiquitination at K196 (P = 0.0331);
MVP
0.76
MPC
0.11
ClinPred
0.97
D
GERP RS
5.5
Varity_R
0.43
gMVP
0.34

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: rs543238078; hg19: chr17-37107866; API