chr9-113169892-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_015258.2(FKBP15):c.2817C>A(p.Ser939Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign 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
FKBP15
NM_015258.2 missense
NM_015258.2 missense
Scores
2
14
Clinical Significance
Conservation
PhyloP100: 1.43
Genes affected
FKBP15 (HGNC:23397): (FKBP prolyl isomerase family member 15) Predicted to enable actin binding activity and peptidyl-prolyl cis-trans isomerase activity. Predicted to be involved in endocytosis and protein peptidyl-prolyl isomerization. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM1
?
In a modified_residue Phosphoserine (size 0) in uniprot entity FKB15_HUMAN
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.10799748).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FKBP15 | NM_015258.2 | c.2817C>A | p.Ser939Arg | missense_variant | 26/28 | ENST00000238256.8 | |
FKBP15 | XM_006717018.3 | c.2787C>A | p.Ser929Arg | missense_variant | 26/28 | ||
FKBP15 | XM_006717019.2 | c.2613C>A | p.Ser871Arg | missense_variant | 25/27 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FKBP15 | ENST00000238256.8 | c.2817C>A | p.Ser939Arg | missense_variant | 26/28 | 1 | NM_015258.2 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1397548Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0AN XY: 689272
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1397548
Hom.:
Cov.:
35
AF XY:
AC XY:
0
AN XY:
689272
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
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Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
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 | Sep 26, 2023 | The c.2817C>A (p.S939R) alteration is located in exon 26 (coding exon 26) of the FKBP15 gene. This alteration results from a C to A substitution at nucleotide position 2817, causing the serine (S) at amino acid position 939 to be replaced by an arginine (R). 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
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
D;D
Sift4G
Benign
T;T
Polyphen
0.43
.;B
Vest4
0.29
MutPred
0.13
.;Loss of phosphorylation at S939 (P = 7e-04);
MVP
MPC
0.26
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at