Variant 6-32129698-T-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.83A>G(p.Asn28Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00434 in 1,614,110 control chromosomes in the GnomAD database, including 38 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 Benign (no stars).

Frequency

Genomes: 𝑓 0.0045 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0043 ( 36 hom. )

Consequence

FKBPL
NM_022110.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.352

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=0.003453523).

BP6

Variant 6-32129698-T-C is Benign according to our data. Variant chr6-32129698-T-C is described in ClinVar as [Benign]. Clinvar id is 3056060.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FKBPL	NM_022110.4 linkuse as main transcript	c.83A>G	p.Asn28Ser	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.83A>G	p.Asn28Ser	missense_variant	2/2	1	NM_022110.4	ENSP00000364298	P1

Frequencies

GnomAD3 genomes

AF:

0.00450

AC:

684

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00633

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00458

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0175

Gnomad SAS

AF:

0.0108

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00271

Gnomad OTH

AF:

0.00575

GnomAD3 exomes

AF:

0.00601

AC:

1510

AN:

251208

Hom.:

AF XY:

0.00604

AC XY:

820

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.00602

Gnomad AMR exome

AF:

0.00492

Gnomad ASJ exome

AF:

0.000694

Gnomad EAS exome

AF:

0.0269

Gnomad SAS exome

AF:

0.0114

Gnomad FIN exome

AF:

0.000647

Gnomad NFE exome

AF:

0.00306

Gnomad OTH exome

AF:

0.00506

GnomAD4 exome

AF:

0.00432

AC:

6314

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00446

AC XY:

3241

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00496

Gnomad4 AMR exome

AF:

0.00561

Gnomad4 ASJ exome

AF:

0.000842

Gnomad4 EAS exome

AF:

0.0147

Gnomad4 SAS exome

AF:

0.0118

Gnomad4 FIN exome

AF:

0.000936

Gnomad4 NFE exome

AF:

0.00352

Gnomad4 OTH exome

AF:

0.00444

GnomAD4 genome

AF:

0.00450

AC:

685

AN:

152218

Hom.:

Cov.:

AF XY:

0.00451

AC XY:

336

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00631

Gnomad4 AMR

AF:

0.00458

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0176

Gnomad4 SAS

AF:

0.0108

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00271

Gnomad4 OTH

AF:

0.00569

Alfa

AF:

0.00430

Hom.:

Bravo

AF:

0.00482

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.00522

AC:

ESP6500EA

AF:

0.00244

AC:

ExAC

AF:

0.00628

AC:

762

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.00322

EpiControl

AF:

0.00338

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

May 13, 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

0.098

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.56

CADD

Benign

6.9

DANN

Benign

0.65

DEOGEN2

Benign

0.0019

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.48

MetaRNN

Benign

0.0035

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.45

REVEL

Benign

0.10

Sift

Benign

0.15

Sift4G

Benign

0.54

Polyphen

0.12

Vest4

0.11

MVP

0.96

MPC

0.34

ClinPred

0.0033

GERP RS

3.0

Varity_R

0.037

gMVP

0.12

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