Variant 7-32988524-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_007270.5(FKBP9):c.911C>T(p.Thr304Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

FKBP9
NM_007270.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.82

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.862

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FKBP9	NM_007270.5 linkuse as main transcript	c.911C>T	p.Thr304Met	missense_variant	6/10	ENST00000242209.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FKBP9	ENST00000242209.9 linkuse as main transcript	c.911C>T	p.Thr304Met	missense_variant	6/10	1	NM_007270.5	P1	O95302-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251118

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135702

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1461618

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

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

May 27, 2022

The c.911C>T (p.T304M) alteration is located in exon 6 (coding exon 6) of the FKBP9 gene. This alteration results from a C to T substitution at nucleotide position 911, causing the threonine (T) at amino acid position 304 to be replaced by a methionine (M). 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

Pathogenic

0.61

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Pathogenic

0.19

CADD

Uncertain

DANN

Pathogenic

1.0

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

1.0

D;D;D;D

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.86

D;D;D;D

MetaSVM

Pathogenic

0.83

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-4.5

D;D;D;D

REVEL

Pathogenic

0.70

Sift

Uncertain

0.015

D;D;D;D

Sift4G

Uncertain

0.0020

D;D;D;D

Polyphen

1.0

.;D;.;.

Vest4

0.86

MutPred

0.66

.;Loss of disorder (P = 0.1016);.;.;

MVP

0.96

MPC

0.30

ClinPred

0.97

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.27

gMVP

0.63

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

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