9-113168536-T-A

Variant names:

• chr9-113168536-T-A
• rs184762226
• NM_015258.2:c.3506A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015258.2(FKBP15):​c.3506A>T​(p.Asp1169Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. D1169G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FKBP15 NM_015258.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.96
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19712648).

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.3506A>T	p.Asp1169Val	missense	Exon 27 of 28	NP_056073.1	Q5T1M5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP15	ENST00000238256.8	TSL:1 MANE Select	c.3506A>T	p.Asp1169Val	missense	Exon 27 of 28	ENSP00000238256.3	Q5T1M5-1
	FKBP15	ENST00000446284.6	TSL:1	c.3506A>T	p.Asp1169Val	missense	Exon 27 of 28	ENSP00000416158.2	Q5T1M5-1
	FKBP15	ENST00000693271.1		c.3488A>T	p.Asp1163Val	missense	Exon 28 of 28	ENSP00000508580.1	A0A8I5KX71

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461606 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727094

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111794

Other (OTH) AF: 0.00 AC: 0 AN: 60366

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.062	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		4.0
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.15
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.95	P
Vest4		0.51
MutPred		0.15		Loss of solvent accessibility (P = 0.0371)
MVP		0.36
MPC		0.68
ClinPred		0.97	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.24
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs184762226; hg19: chr9-115930816;