rs137853864

Positions:

• chr15-64162961-A-C
• chr15-64162961-A-G
• chr15-64162961-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_000942.5(PPIB):​c.26T>G​(p.Met9Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPIB NM_000942.5 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1 O:1
• Conservation: PhyloP100: 4.25

Genes affected

PPIB (HGNC:9255): (peptidylprolyl isomerase B) The protein encoded by this gene is a cyclosporine-binding protein and is mainly located within the endoplasmic reticulum. It is associated with the secretory pathway and released in biological fluids. This protein can bind to cells derived from T- and B-lymphocytes, and may regulate cyclosporine A-mediated immunosuppression. Variants have been identified in this protein that give rise to recessive forms of osteogenesis imperfecta. [provided by RefSeq, Oct 2009]

PPIB (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 15-64162961-A-C is Pathogenic according to our data. Variant chr15-64162961-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 16927.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPIB	NM_000942.5	c.26T>G	p.Met9Arg	missense_variant	1/5	ENST00000300026.4	NP_000933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPIB	ENST00000300026.4	c.26T>G	p.Met9Arg	missense_variant	1/5	1	NM_000942.5	ENSP00000300026.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Osteogenesis imperfecta type 9 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 20, 2010

- -

not provided Other:1

not provided, no classification provided

curation

Osteogenesis Imperfecta Variant Database (PPIB)

Feb 17, 2011

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.39	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.082	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.49
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.052	T
Polyphen		0.97	D
Vest4		0.43
MutPred		0.74		Gain of methylation at K10 (P = 0.0276);
MVP		0.92
MPC		0.81
ClinPred		0.97	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.89
gMVP		0.90

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

LitVar

Other links and lift over

dbSNP: rs137853864; hg19: chr15-64455160;