7-32957595-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007270.5(FKBP9):​c.22C>T​(p.Pro8Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000151 in 1,321,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

FKBP9
NM_007270.5 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0780
Variant links:
Genes affected
FKBP9 (HGNC:3725): (FKBP prolyl isomerase 9) Predicted to enable calcium ion binding activity. Predicted to be involved in protein folding. Predicted to be located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

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=0.13726622).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FKBP9NM_007270.5 linkc.22C>T p.Pro8Ser missense_variant Exon 1 of 10 ENST00000242209.9 NP_009201.2 O95302-1A7YQ73
FKBP9NM_001284341.2 linkc.22C>T p.Pro8Ser missense_variant Exon 1 of 11 NP_001271270.1 O95302-3A7YQ73
FKBP9XM_011515115.4 linkc.22C>T p.Pro8Ser missense_variant Exon 1 of 7 XP_011513417.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FKBP9ENST00000242209.9 linkc.22C>T p.Pro8Ser missense_variant Exon 1 of 10 1 NM_007270.5 ENSP00000242209.4 O95302-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000151
AC:
2
AN:
1321242
Hom.:
0
Cov.:
31
AF XY:
0.00000307
AC XY:
2
AN XY:
650882
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000394
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000138
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 10, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.22C>T (p.P8S) alteration is located in exon 1 (coding exon 1) of the FKBP9 gene. This alteration results from a C to T substitution at nucleotide position 22, causing the proline (P) at amino acid position 8 to be replaced by a serine (S). 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
0.085
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
17
DANN
Benign
0.97
DEOGEN2
Benign
0.0070
.;T
Eigen
Benign
-0.64
Eigen_PC
Benign
-0.51
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.48
T;T
M_CAP
Pathogenic
0.52
D
MetaRNN
Benign
0.14
T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
0.0
N;N
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
0.35
N;N
REVEL
Benign
0.057
Sift
Benign
0.44
T;T
Sift4G
Uncertain
0.048
D;T
Polyphen
0.0
.;B
Vest4
0.20
MutPred
0.45
Loss of catalytic residue at P8 (P = 0.0172);Loss of catalytic residue at P8 (P = 0.0172);
MVP
0.52
MPC
0.74
ClinPred
0.081
T
GERP RS
3.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.7
Varity_R
0.031
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-32997207; API