chr9-113170581-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_015258.2(FKBP15):c.2707G>A(p.Glu903Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000753 in 1,461,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
FKBP15
NM_015258.2 missense
NM_015258.2 missense
Scores
3
3
10
Clinical Significance
Conservation
PhyloP100: 5.65
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 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.22005862).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FKBP15 | NM_015258.2 | c.2707G>A | p.Glu903Lys | missense_variant | 25/28 | ENST00000238256.8 | |
FKBP15 | XM_006717018.3 | c.2677G>A | p.Glu893Lys | missense_variant | 25/28 | ||
FKBP15 | XM_006717019.2 | c.2503G>A | p.Glu835Lys | missense_variant | 24/27 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FKBP15 | ENST00000238256.8 | c.2707G>A | p.Glu903Lys | missense_variant | 25/28 | 1 | NM_015258.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152206Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249254Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135220
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GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461566Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7AN XY: 727068
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.00000657 AC: 1AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74356
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?
Data not reliable, filtered out with message: AS_VQSR
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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 27, 2023 | The c.2707G>A (p.E903K) alteration is located in exon 25 (coding exon 25) of the FKBP15 gene. This alteration results from a G to A substitution at nucleotide position 2707, causing the glutamic acid (E) at amino acid position 903 to be replaced by a lysine (K). 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
Pathogenic
Dann
Pathogenic
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Benign
T;T
Polyphen
0.98
.;D
Vest4
0.65
MutPred
0.40
.;Gain of MoRF binding (P = 0.0065);
MVP
MPC
0.41
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
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