17-38951613-C-A
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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
NM_001008777.3 missense
Scores
3
10
6
Clinical Significance
Conservation
PhyloP100: 3.29
Genes affected
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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, 0.775
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FBXO47 | NM_001008777.3 | c.584G>T | p.Arg195Leu | missense_variant | 6/11 | ENST00000378079.3 | NP_001008777.2 | |
FBXO47 | XM_011524865.3 | c.506G>T | p.Arg169Leu | missense_variant | 6/11 | XP_011523167.1 | ||
FBXO47 | XM_011524866.4 | c.413G>T | p.Arg138Leu | missense_variant | 5/10 | XP_011523168.1 | ||
FBXO47 | XM_011524867.3 | c.584G>T | p.Arg195Leu | missense_variant | 6/10 | XP_011523169.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FBXO47 | ENST00000378079.3 | c.584G>T | p.Arg195Leu | missense_variant | 6/11 | 1 | NM_001008777.3 | ENSP00000367319 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251272Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135820
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461444Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 727048
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
ExAC
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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 submitter | clinical testing | Ambry Genetics | Feb 17, 2024 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of ubiquitination at K196 (P = 0.0331);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at