9-113169230-C-A

Variant names:

• chr9-113169230-C-A
• rs375508657
• NM_015258.2:c.3479G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015258.2(FKBP15):​c.3479G>T​(p.Arg1160Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R1160H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FKBP15 NM_015258.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.401
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.042104006).

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.3479G>T	p.Arg1160Leu	missense	Exon 26 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.3479G>T	p.Arg1160Leu	missense	Exon 26 of 28	ENSP00000238256.3	Q5T1M5-1
	FKBP15	ENST00000446284.6	TSL:1	c.3479G>T	p.Arg1160Leu	missense	Exon 26 of 28	ENSP00000416158.2	Q5T1M5-1
	FKBP15	ENST00000693271.1		c.3461G>T	p.Arg1154Leu	missense	Exon 27 of 28	ENSP00000508580.1	A0A8I5KX71

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.16
DANN	Benign	0.78
DEOGEN2	Benign	0.00092	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.40
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.018
Sift	Uncertain	0.020	D
Sift4G	Benign	0.29	T
Polyphen		0.057	B
Vest4		0.15
MutPred		0.18		Loss of loop (P = 0.0603)
MVP		0.067
MPC		0.20
ClinPred		0.046	T
GERP RS		-0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.049
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs375508657; hg19: chr9-115931510; COSMIC: COSV99439864;