Variant 7-73331735-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_003602.5(FKBP6):c.547C>T(p.Arg183Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00444 in 1,613,296 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0026 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0046 ( 24 hom. )

Consequence

FKBP6
NM_003602.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.43

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=0.034024477).

BP6

Variant 7-73331735-C-T is Benign according to our data. Variant chr7-73331735-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2657551.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FKBP6	NM_003602.5 linkuse as main transcript	c.547C>T	p.Arg183Cys	missense_variant	5/9	ENST00000252037.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FKBP6	ENST00000252037.5 linkuse as main transcript	c.547C>T	p.Arg183Cys	missense_variant	5/9	1	NM_003602.5	P4	O75344-1

Frequencies

GnomAD3 genomes

AF:

0.00264

AC:

401

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00482

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00297

AC:

740

AN:

249554

Hom.:

AF XY:

0.00292

AC XY:

396

AN XY:

135398

show subpopulations

Gnomad AFR exome

AF:

0.000839

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00348

Gnomad NFE exome

AF:

0.00555

Gnomad OTH exome

AF:

0.00198

GnomAD4 exome

AF:

0.00463

AC:

6763

AN:

1461098

Hom.:

Cov.:

AF XY:

0.00458

AC XY:

3329

AN XY:

726872

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00346

Gnomad4 NFE exome

AF:

0.00572

Gnomad4 OTH exome

AF:

0.00291

GnomAD4 genome

AF:

0.00263

AC:

401

AN:

152198

Hom.:

Cov.:

AF XY:

0.00239

AC XY:

178

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.000867

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00283

Gnomad4 NFE

AF:

0.00483

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00430

Hom.:

Bravo

AF:

0.00270

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.000269

AC:

ESP6500EA

AF:

0.00415

AC:

ExAC

AF:

0.00315

AC:

381

EpiCase

AF:

0.00469

EpiControl

AF:

0.00421

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2024

FKBP6: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.071

BayesDel_noAF

Pathogenic

0.14

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.57

.;.;D

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.081

MetaRNN

Benign

0.034

T;T;T

MetaSVM

Uncertain

0.019

MutationAssessor

Uncertain

2.1

.;.;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.4

D;D;D

REVEL

Pathogenic

0.67

Sift

Uncertain

0.019

D;D;D

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.81

MVP

0.88

MPC

0.99

ClinPred

0.026

GERP RS

5.5

Varity_R

0.14

gMVP

0.42

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