Variant chr7-32996262-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_007270.5(FKBP9):c.1139C>G(p.Pro380Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

FKBP9
NM_007270.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.27

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 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=0.08718923).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FKBP9	NM_007270.5 linkuse as main transcript	c.1139C>G	p.Pro380Arg	missense_variant	7/10	ENST00000242209.9
FKBP9	NM_001284341.2 linkuse as main transcript	c.1298C>G	p.Pro433Arg	missense_variant	8/11
FKBP9	NM_001284343.2 linkuse as main transcript	c.443C>G	p.Pro148Arg	missense_variant	4/7
FKBP9	XM_047419849.1 linkuse as main transcript	c.860C>G	p.Pro287Arg	missense_variant	7/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FKBP9	ENST00000242209.9 linkuse as main transcript	c.1139C>G	p.Pro380Arg	missense_variant	7/10	1	NM_007270.5	P1	O95302-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251486

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461810

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000412

AC:

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

Mar 31, 2022

The c.1139C>G (p.P380R) alteration is located in exon 7 (coding exon 7) of the FKBP9 gene. This alteration results from a C to G substitution at nucleotide position 1139, causing the proline (P) at amino acid position 380 to be replaced by an arginine (R). 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

0.074

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.88

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.79

T;T;T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.087

T;T;T;T

MetaSVM

Benign

-0.94

MutationTaster

Benign

0.73

N;N;N;N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.78

N;N;N;N

REVEL

Benign

0.077

Sift

Benign

0.077

T;T;T;T

Sift4G

Benign

0.27

T;T;T;T

Polyphen

0.044

.;B;.;.

Vest4

0.22

MutPred

0.54

.;Loss of catalytic residue at P379 (P = 0.0101);.;.;

MVP

0.60

MPC

0.067

ClinPred

0.068

GERP RS

4.0

Varity_R

0.062

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over