Variant 9-113169398-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015258.2(FKBP15):c.3311A>G(p.Glu1104Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000266 in 1,614,028 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00026 ( 1 hom. )

Consequence

FKBP15
NM_015258.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.546

Variant links:

Genes affected

FKBP15 (HGNC:23397): (FKBP prolyl isomerase family member 15) Predicted to enable actin binding activity and peptidyl-prolyl cis-trans isomerase activity. Predicted to be involved in endocytosis and protein peptidyl-prolyl isomerization. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

FKBP15 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.020121962).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FKBP15	NM_015258.2 linkuse as main transcript	c.3311A>G	p.Glu1104Gly	missense_variant	26/28	ENST00000238256.8
FKBP15	XM_006717018.3 linkuse as main transcript	c.3281A>G	p.Glu1094Gly	missense_variant	26/28
FKBP15	XM_006717019.2 linkuse as main transcript	c.3107A>G	p.Glu1036Gly	missense_variant	25/27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FKBP15	ENST00000238256.8 linkuse as main transcript	c.3311A>G	p.Glu1104Gly	missense_variant	26/28	1	NM_015258.2	P2	Q5T1M5-1

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000329

AC:

AN:

249236

Hom.:

AF XY:

0.000348

AC XY:

AN XY:

135204

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000167

Gnomad SAS exome

AF:

0.000686

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000434

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.000265

AC:

387

AN:

1461690

Hom.:

Cov.:

AF XY:

0.000303

AC XY:

220

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000765

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.000267

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000276

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.000295

AC XY:

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000319

Hom.:

Bravo

AF:

0.000189

ExAC

AF:

0.000372

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000763

EpiControl

AF:

0.000593

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

Nov 07, 2022

The c.3311A>G (p.E1104G) alteration is located in exon 26 (coding exon 26) of the FKBP15 gene. This alteration results from a A to G substitution at nucleotide position 3311, causing the glutamic acid (E) at amino acid position 1104 to be replaced by a glycine (G). 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

0.080

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.66

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.10

M_CAP

Benign

0.0065

MetaRNN

Benign

0.020

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.81

N;N

REVEL

Benign

0.043

Sift

Uncertain

0.014

D;D

Sift4G

Benign

0.32

T;T

Polyphen

0.018

.;B

Vest4

0.034

MVP

0.25

MPC

0.18

ClinPred

0.017

GERP RS

3.9

Varity_R

0.074

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