Genetic Variant FKBP9:p.Pro10Leu (chr7-32957602-C-T) – 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.29C>T(p.Pro10Leu) 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. 13/22 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. P10Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FKBP9
NM_007270.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.499

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=0.15700278).

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.29C>T	p.Pro10Leu	missense	Exon 1 of 10	NP_009201.2
	FKBP9	NM_001284341.2		c.29C>T	p.Pro10Leu	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.29C>T	p.Pro10Leu	missense	Exon 1 of 10	ENSP00000242209.4	O95302-1
FKBP9	ENST00000538336.5	TSL:2	c.29C>T	p.Pro10Leu	missense	Exon 1 of 11	ENSP00000439250.1	O95302-3
FKBP9	ENST00000875466.1		c.29C>T	p.Pro10Leu	missense	Exon 1 of 11	ENSP00000545525.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1323536

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

652106

African (AFR)

AF:

0.00

AC:

AN:

26590

American (AMR)

AF:

0.00

AC:

AN:

25582

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23166

East Asian (EAS)

AF:

0.00

AC:

AN:

28618

South Asian (SAS)

AF:

0.00

AC:

AN:

72730

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33030

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4442

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1054346

Other (OTH)

AF:

0.00

AC:

AN:

55032

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0069

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.59

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

0.50

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

0.55

REVEL

Benign

0.027

Sift

Uncertain

0.020

Sift4G

Benign

0.40

Polyphen

0.0

Vest4

0.40

MutPred

0.42

Loss of glycosylation at P10 (P = 9e-04)

MVP

0.36

MPC

0.76

ClinPred

0.60

GERP RS

2.0

PromoterAI

-0.036

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Varity_R

0.041

gMVP

0.28

Mutation Taster

=88/12

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