15-64156107-GCTGT-G
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Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_000942.5(PPIB):c.563_566delACAG(p.Asp188fs) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000137 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
PPIB
NM_000942.5 frameshift
NM_000942.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.74
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]
SNX22 (HGNC:16315): (sorting nexin 22) The protein encoded by this gene is a sorting nexin that is found in the cytoplasm, where it interacts with membrane-bound phosphatidylinositol 3-phosphate. The encoded protein may play a role in intracellular trafficking. Two transcript variants, one protein-coding and the other not protein-coding, have been found for this gene. [provided by RefSeq, Dec 2012]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.135 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 15-64156107-GCTGT-G is Pathogenic according to our data. Variant chr15-64156107-GCTGT-G is described in ClinVar as [Pathogenic]. Clinvar id is 41422.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.563_566delACAG | p.Asp188fs | frameshift_variant | 5/5 | ENST00000300026.4 | NP_000933.1 | |
SNX22 | NM_024798.3 | c.*1606_*1609delGTCT | 3_prime_UTR_variant | 7/7 | ENST00000325881.9 | NP_079074.2 | ||
SNX22 | XM_017022581.2 | c.*1606_*1609delGTCT | 3_prime_UTR_variant | 6/6 | XP_016878070.1 | |||
SNX22 | NR_073534.2 | n.2280_2283delGTCT | non_coding_transcript_exon_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PPIB | ENST00000300026.4 | c.563_566delACAG | p.Asp188fs | frameshift_variant | 5/5 | 1 | NM_000942.5 | ENSP00000300026.4 | ||
SNX22 | ENST00000325881.9 | c.*1606_*1609delGTCT | 3_prime_UTR_variant | 7/7 | 1 | NM_024798.3 | ENSP00000323435.4 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00000798 AC: 2AN: 250656Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135550
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461872Hom.: 0 AF XY: 0.00000275 AC XY: 2AN XY: 727236
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GnomAD4 genome Cov.: 31
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Osteogenesis imperfecta type 9 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 2012 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at