Variant chr6-32129513-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_022110.4(FKBPL):c.268G>A(p.Ala90Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,614,130 control chromosomes in the GnomAD database, including 9,611 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 Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.11 ( 1082 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8529 hom. )

Consequence

FKBPL
NM_022110.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.170

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013205111).

BP6

Variant 6-32129513-C-T is Benign according to our data. Variant chr6-32129513-C-T is described in ClinVar as [Benign]. Clinvar id is 3060339.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FKBPL	NM_022110.4 linkuse as main transcript	c.268G>A	p.Ala90Thr	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.268G>A	p.Ala90Thr	missense_variant	2/2	1	NM_022110.4	ENSP00000364298	P1

Frequencies

GnomAD3 genomes

AF:

0.113

AC:

17183

AN:

152130

Hom.:

1087

Cov.:

show subpopulations

Gnomad AFR

AF:

0.154

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.0802

Gnomad ASJ

AF:

0.126

Gnomad EAS

AF:

0.0387

Gnomad SAS

AF:

0.157

Gnomad FIN

AF:

0.0557

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.105

Gnomad OTH

AF:

0.112

GnomAD3 exomes

AF:

0.0950

AC:

23876

AN:

251436

Hom.:

1399

AF XY:

0.0981

AC XY:

13326

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.163

Gnomad AMR exome

AF:

0.0640

Gnomad ASJ exome

AF:

0.130

Gnomad EAS exome

AF:

0.0360

Gnomad SAS exome

AF:

0.136

Gnomad FIN exome

AF:

0.0547

Gnomad NFE exome

AF:

0.0973

Gnomad OTH exome

AF:

0.106

GnomAD4 exome

AF:

0.103

AC:

149938

AN:

1461882

Hom.:

8529

Cov.:

AF XY:

0.103

AC XY:

74941

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.168

Gnomad4 AMR exome

AF:

0.0695

Gnomad4 ASJ exome

AF:

0.132

Gnomad4 EAS exome

AF:

0.0226

Gnomad4 SAS exome

AF:

0.137

Gnomad4 FIN exome

AF:

0.0553

Gnomad4 NFE exome

AF:

0.104

Gnomad4 OTH exome

AF:

0.106

GnomAD4 genome

AF:

0.113

AC:

17181

AN:

152248

Hom.:

1082

Cov.:

AF XY:

0.111

AC XY:

8234

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.154

Gnomad4 AMR

AF:

0.0800

Gnomad4 ASJ

AF:

0.126

Gnomad4 EAS

AF:

0.0390

Gnomad4 SAS

AF:

0.157

Gnomad4 FIN

AF:

0.0557

Gnomad4 NFE

AF:

0.105

Gnomad4 OTH

AF:

0.111

Alfa

AF:

0.108

Hom.:

1420

Bravo

AF:

0.117

TwinsUK

AF:

0.0930

AC:

345

ALSPAC

AF:

0.0999

AC:

385

ESP6500AA

AF:

0.148

AC:

652

ESP6500EA

AF:

0.110

AC:

942

ExAC

AF:

0.0983

AC:

11930

Asia WGS

AF:

0.0720

AC:

252

AN:

3478

EpiCase

AF:

0.112

EpiControl

AF:

0.105

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

FKBPL-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

This variant is classified as 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

0.065

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0013

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.37

MetaRNN

Benign

0.0013

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.17

REVEL

Benign

0.16

Sift

Benign

0.20

Sift4G

Benign

0.35

Polyphen

0.0050

Vest4

0.026

MPC

0.41

ClinPred

0.0027

GERP RS

2.5

Varity_R

0.023

gMVP

0.25

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