dbSNP rs1280574242: FKBP9:p.Pro8Thr (chr7-32957595-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007270.5(FKBP9):c.22C>A(p.Pro8Thr) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P8S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.6e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FKBP9
NM_007270.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0780

Publications

0 publications found

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]

FKBP9 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14195424).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007270.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP9	NM_007270.5	MANE Select	c.22C>A	p.Pro8Thr	missense	Exon 1 of 10	NP_009201.2
	FKBP9	NM_001284341.2		c.22C>A	p.Pro8Thr	missense	Exon 1 of 11	NP_001271270.1	O95302-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FKBP9	ENST00000242209.9	TSL:1 MANE Select	c.22C>A	p.Pro8Thr	missense	Exon 1 of 10	ENSP00000242209.4	O95302-1
FKBP9	ENST00000538336.5	TSL:2	c.22C>A	p.Pro8Thr	missense	Exon 1 of 11	ENSP00000439250.1	O95302-3
FKBP9	ENST00000875466.1		c.22C>A	p.Pro8Thr	missense	Exon 1 of 11	ENSP00000545525.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000137

AC:

AN:

72856

AF XY:

0.0000237

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000371

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

7.57e-7

AC:

AN:

1321242

Hom.:

Cov.:

AF XY:

0.00000154

AC XY:

AN XY:

650882

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26550

American (AMR)

AF:

0.00

AC:

AN:

25396

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23034

East Asian (EAS)

AF:

0.00

AC:

AN:

28564

South Asian (SAS)

AF:

0.00

AC:

AN:

72394

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32864

Middle Eastern (MID)

AF:

0.000237

AC:

AN:

4220

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1053310

Other (OTH)

AF:

0.00

AC:

AN:

54910

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.0071

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.53

M_CAP

Pathogenic

0.48

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

PhyloP100

-0.078

PrimateAI

Uncertain

0.79

PROVEAN

Benign

0.13

REVEL

Benign

0.059

Sift

Benign

0.29

Sift4G

Uncertain

0.036

Polyphen

0.0070

Vest4

0.24

MutPred

0.44

Loss of glycosylation at P8 (P = 0.0085)

MVP

0.50

MPC

0.82

ClinPred

0.039

GERP RS

3.0

PromoterAI

-0.066

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.039

gMVP

0.37

Mutation Taster

=84/16

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over