Variant chr6-32129644-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_022110.4(FKBPL):c.137C>G(p.Thr46Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,614,134 control chromosomes in the GnomAD database, including 117 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0093 ( 9 hom., cov: 32)

Exomes 𝑓: 0.012 ( 108 hom. )

Consequence

FKBPL
NM_022110.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.112

Variant links:

Genes affected

FKBPL (HGNC:13949): (FKBP prolyl isomerase like) The protein encoded by this gene has similarity to the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. The encoded protein is thought to have a potential role in the induced radioresistance. Also it appears to have some involvement in the control of the cell cycle. [provided by RefSeq, Jul 2008]

FKBPL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0046557486).

BP6

Variant 6-32129644-G-C is Benign according to our data. Variant chr6-32129644-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3041863.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FKBPL	NM_022110.4 linkuse as main transcript	c.137C>G	p.Thr46Arg	missense_variant	2/2	ENST00000375156.4	NP_071393.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKBPL	ENST00000375156.4 linkuse as main transcript	c.137C>G	p.Thr46Arg	missense_variant	2/2	1	NM_022110.4	ENSP00000364298	P1

Frequencies

GnomAD3 genomes

AF:

0.00930

AC:

1415

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00167

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0104

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.0208

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0137

Gnomad OTH

AF:

0.0139

GnomAD3 exomes

AF:

0.0102

AC:

2562

AN:

251496

Hom.:

AF XY:

0.0104

AC XY:

1414

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.00679

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00199

Gnomad FIN exome

AF:

0.0204

Gnomad NFE exome

AF:

0.0153

Gnomad OTH exome

AF:

0.00977

GnomAD4 exome

AF:

0.0118

AC:

17276

AN:

1461888

Hom.:

108

Cov.:

AF XY:

0.0116

AC XY:

8450

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00161

Gnomad4 AMR exome

AF:

0.00680

Gnomad4 ASJ exome

AF:

0.000497

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00206

Gnomad4 FIN exome

AF:

0.0199

Gnomad4 NFE exome

AF:

0.0135

Gnomad4 OTH exome

AF:

0.0108

GnomAD4 genome

AF:

0.00929

AC:

1415

AN:

152246

Hom.:

Cov.:

AF XY:

0.00930

AC XY:

692

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00166

Gnomad4 AMR

AF:

0.0104

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.0208

Gnomad4 NFE

AF:

0.0137

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.00863

Hom.:

Bravo

AF:

0.00835

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.0156

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.0122

AC:

105

ExAC

AF:

0.0103

AC:

1249

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0107

EpiControl

AF:

0.0106

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

FKBPL-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 21, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.53

CADD

Benign

5.5

DANN

Benign

0.97

DEOGEN2

Benign

0.0024

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.30

MetaRNN

Benign

0.0047

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.1

REVEL

Benign

0.13

Sift

Benign

0.050

Sift4G

Benign

0.21

Polyphen

0.26

Vest4

0.25

MPC

0.59

ClinPred

0.0066

GERP RS

1.8

Varity_R

0.062

gMVP

0.33

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