rs137853865
Variant names:
Variant summary
Our verdict is Likely pathogenic. The variant received 9 ACMG points: 9P and 0B. PVS1PP5
The NM_000942.5(PPIB):c.120delC(p.Val42SerfsTer16) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,459,396 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
PPIB
NM_000942.5 frameshift
NM_000942.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.63
Publications
2 publications found
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 Gene-Disease associations (from GenCC):
- osteogenesis imperfecta type 9Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
- osteogenesis imperfecta type 2Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- osteogenesis imperfecta type 3Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- osteogenesis imperfecta type 4Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 9 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
Variant 15-64162866-TG-T is Pathogenic according to our data. Variant chr15-64162866-TG-T is described in ClinVar as Pathogenic. ClinVar VariationId is 31843.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000942.5. 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 |
|---|---|---|---|---|---|---|---|---|---|
| PPIB | NM_000942.5 | MANE Select | c.120delC | p.Val42SerfsTer16 | frameshift | Exon 1 of 5 | NP_000933.1 | P23284 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PPIB | ENST00000300026.4 | TSL:1 MANE Select | c.120delC | p.Val42SerfsTer16 | frameshift | Exon 1 of 5 | ENSP00000300026.4 | P23284 | |
| PPIB | ENST00000561048.2 | TSL:1 | n.153delC | non_coding_transcript_exon | Exon 1 of 4 | ||||
| PPIB | ENST00000851557.1 | c.120delC | p.Val42SerfsTer16 | frameshift | Exon 1 of 5 | ENSP00000521616.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1459396Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9AN XY: 725754 show subpopulations
GnomAD4 exome
AF:
AC:
15
AN:
1459396
Hom.:
Cov.:
32
AF XY:
AC XY:
9
AN XY:
725754
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33440
American (AMR)
AF:
AC:
0
AN:
44504
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26056
East Asian (EAS)
AF:
AC:
0
AN:
39628
South Asian (SAS)
AF:
AC:
0
AN:
85704
European-Finnish (FIN)
AF:
AC:
0
AN:
52956
Middle Eastern (MID)
AF:
AC:
0
AN:
5650
European-Non Finnish (NFE)
AF:
AC:
15
AN:
1111212
Other (OTH)
AF:
AC:
0
AN:
60246
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.465
Heterozygous variant carriers
0
1
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0.40
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
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55-60
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Osteogenesis imperfecta type 9 (1)
-
-
-
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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