Genetic Variant FKBP9:p.Phe71Cys (chr7-32957785-T-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_007270.5(FKBP9):c.212T>G(p.Phe71Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000232 in 1,452,246 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

FKBP9
NM_007270.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.39

Publications

2 publications found

Variant links:

Genes affected

FKBP9 (HGNC:3725): (FKBP prolyl isomerase 9) Predicted to enable calcium ion binding activity. Predicted to be involved in protein folding. Predicted to be located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

FKBP9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.807

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007270.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP9	NM_007270.5	MANE Select	c.212T>G	p.Phe71Cys	missense	Exon 1 of 10	NP_009201.2
	FKBP9	NM_001284341.2		c.212T>G	p.Phe71Cys	missense	Exon 1 of 11	NP_001271270.1	O95302-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FKBP9	ENST00000242209.9	TSL:1 MANE Select	c.212T>G	p.Phe71Cys	missense	Exon 1 of 10	ENSP00000242209.4	O95302-1
FKBP9	ENST00000538336.5	TSL:2	c.212T>G	p.Phe71Cys	missense	Exon 1 of 11	ENSP00000439250.1	O95302-3
FKBP9	ENST00000875466.1		c.212T>G	p.Phe71Cys	missense	Exon 1 of 11	ENSP00000545525.1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000541

AC:

AN:

110930

AF XY:

0.0000476

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000105

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000246

AC:

320

AN:

1299898

Hom.:

Cov.:

AF XY:

0.000222

AC XY:

141

AN XY:

636454

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26458

American (AMR)

AF:

0.00

AC:

AN:

22760

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19310

East Asian (EAS)

AF:

0.00

AC:

AN:

31046

South Asian (SAS)

AF:

0.00

AC:

AN:

65564

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5230

European-Non Finnish (NFE)

AF:

0.000297

AC:

308

AN:

1035848

Other (OTH)

AF:

0.000225

AC:

AN:

53274

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000112

AC:

AN:

152348

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.0000721

AC:

AN:

41592

American (AMR)

AF:

0.00

AC:

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000140

Hom.:

Bravo

AF:

0.0000831

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000598

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Uncertain

0.029

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.39

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.86

M_CAP

Pathogenic

0.55

MetaRNN

Pathogenic

0.81

MetaSVM

Uncertain

0.78

MutationAssessor

Pathogenic

4.8

PhyloP100

2.4

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-4.5

REVEL

Pathogenic

0.71

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.55

MVP

0.96

MPC

2.1

ClinPred

0.99

GERP RS

2.3

PromoterAI

-0.0012

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.75

gMVP

0.72

Mutation Taster

=43/57

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over