Genetic Variant FKBP6:p.Arg36Gln (chr7-73328624-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003602.5(FKBP6):c.107G>A(p.Arg36Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00289 in 1,610,476 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 11 hom. )

Consequence

FKBP6
NM_003602.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.93

Variant links:

Genes affected

FKBP6 (HGNC:3722): (FKBP prolyl isomerase family member 6 (inactive)) The protein encoded by this gene is a cis-trans peptidyl-prolyl isomerase that may function in immunoregulation and basic cellular processes involving protein folding and trafficking. This gene is located in a chromosomal region that is deleted in Williams-Beuren syndrome. Defects in this gene may cause male infertility. There are multiple pseudogenes for this gene located nearby on chromosome 7. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

FKBP6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005741358).

BP6

Variant 7-73328624-G-A is Benign according to our data. Variant chr7-73328624-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3770716.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-73328624-G-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP6	NM_003602.5 link	c.107G>A	p.Arg36Gln	missense_variant	Exon 2 of 9	ENST00000252037.5	NP_003593.3	O75344-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP6	ENST00000252037.5 link	c.107G>A	p.Arg36Gln	missense_variant	Exon 2 of 9	1	NM_003602.5	ENSP00000252037.4		O75344-1

Frequencies

GnomAD3 genomes

AF:

0.00191

AC:

290

AN:

151864

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000629

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00427

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00256

Gnomad OTH

AF:

0.00672

GnomAD3 exomes

AF:

0.00197

AC:

426

AN:

216660

Hom.:

AF XY:

0.00185

AC XY:

220

AN XY:

118724

show subpopulations

Gnomad AFR exome

AF:

0.000168

Gnomad AMR exome

AF:

0.00431

Gnomad ASJ exome

AF:

0.000216

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000700

Gnomad FIN exome

AF:

0.000503

Gnomad NFE exome

AF:

0.00255

Gnomad OTH exome

AF:

0.00638

GnomAD4 exome

AF:

0.00300

AC:

4372

AN:

1458494

Hom.:

Cov.:

AF XY:

0.00284

AC XY:

2064

AN XY:

725650

show subpopulations

Gnomad4 AFR exome

AF:

0.000419

Gnomad4 AMR exome

AF:

0.00472

Gnomad4 ASJ exome

AF:

0.000268

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000105

Gnomad4 FIN exome

AF:

0.000431

Gnomad4 NFE exome

AF:

0.00346

Gnomad4 OTH exome

AF:

0.00397

GnomAD4 genome

AF:

0.00191

AC:

290

AN:

151982

Hom.:

Cov.:

AF XY:

0.00183

AC XY:

136

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.000627

Gnomad4 AMR

AF:

0.00426

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00256

Gnomad4 OTH

AF:

0.00665

Alfa

AF:

0.00196

Hom.:

Bravo

AF:

0.00252

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00111

AC:

ExAC

AF:

0.00156

AC:

186

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FKBP6: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.084

.;.;.;T

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.77

T;T;T;T

MetaRNN

Benign

0.0057

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.63

.;.;N;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.23

N;N;N;N

REVEL

Benign

0.027

Sift

Benign

0.46

T;T;T;T

Sift4G

Benign

0.39

T;T;T;T

Polyphen

0.091

B;.;.;B

Vest4

0.16

MVP

0.47

MPC

2.1

ClinPred

0.011

GERP RS

1.9

Varity_R

0.069

gMVP

0.48

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