Genetic Variant FKBP15:p.Gly1105Glu (chr9-113169395-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_015258.2(FKBP15):c.3314G>A(p.Gly1105Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,461,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1105A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

FKBP15
NM_015258.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.99

Publications

2 publications found

Variant links:

Genes affected

FKBP15 (HGNC:23397): (FKBP prolyl isomerase family member 15) Predicted to enable actin binding activity and peptidyl-prolyl cis-trans isomerase activity. Predicted to be involved in endocytosis and protein peptidyl-prolyl isomerization. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

FKBP15 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.029821426).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015258.2. 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
	FKBP15	NM_015258.2	MANE Select	c.3314G>A	p.Gly1105Glu	missense	Exon 26 of 28	NP_056073.1	Q5T1M5-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FKBP15	ENST00000238256.8	TSL:1 MANE Select	c.3314G>A	p.Gly1105Glu	missense	Exon 26 of 28	ENSP00000238256.3	Q5T1M5-1
FKBP15	ENST00000446284.6	TSL:1	c.3314G>A	p.Gly1105Glu	missense	Exon 26 of 28	ENSP00000416158.2	Q5T1M5-1
FKBP15	ENST00000693271.1		c.3296G>A	p.Gly1099Glu	missense	Exon 27 of 28	ENSP00000508580.1	A0A8I5KX71

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000241

AC:

AN:

249242

AF XY:

0.0000444

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1461690

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727128

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000209

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111856

Other (OTH)

AF:

0.00

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.69

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.0014

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.65

M_CAP

Benign

0.0042

MetaRNN

Benign

0.030

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.4

PhyloP100

-2.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.47

REVEL

Benign

0.055

Sift

Benign

0.70

Sift4G

Benign

0.97

Polyphen

0.0010

Vest4

0.077

MutPred

0.057

Gain of solvent accessibility (P = 0.0456)

MVP

0.13

MPC

0.20

ClinPred

0.019

GERP RS

-4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.034

Mutation Taster

=96/4

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over