Genetic Variant PPIB:c.*189dupG (chr15-64155833-A-AC) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_000942.5(PPIB):c.*189dupG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000396 in 792,722 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00040 ( 1 hom. )

Consequence

PPIB
NM_000942.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00700

Publications

0 publications found

Variant links:

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 links:

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]

SNX22 links:

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ACMG classification

Classification was made for transcript

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

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PPIB	NM_000942.5	MANE Select	c.*189dupG	3_prime_UTR	Exon 5 of 5	NP_000933.1	P23284
SNX22	NM_024798.3	MANE Select	c.*1328dupC	3_prime_UTR	Exon 7 of 7	NP_079074.2	Q96L94-1
SNX22	NR_073534.2		n.2002dupC	non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PPIB	ENST00000300026.4	TSL:1 MANE Select	c.*189dupG	3_prime_UTR	Exon 5 of 5	ENSP00000300026.4	P23284
SNX22	ENST00000325881.9	TSL:1 MANE Select	c.*1328dupC	3_prime_UTR	Exon 7 of 7	ENSP00000323435.4	Q96L94-1
SNX22	ENST00000560997.1	TSL:1	n.1723dupC	non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.000373

AC:

AN:

147590

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000678

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00381

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000241

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000402

AC:

259

AN:

645018

Hom.:

Cov.:

AF XY:

0.000337

AC XY:

113

AN XY:

335308

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15384

American (AMR)

AF:

0.00

AC:

AN:

20290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16508

East Asian (EAS)

AF:

0.00

AC:

AN:

31086

South Asian (SAS)

AF:

0.00

AC:

AN:

54252

European-Finnish (FIN)

AF:

0.00557

AC:

169

AN:

30316

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2414

European-Non Finnish (NFE)

AF:

0.000149

AC:

AN:

442482

Other (OTH)

AF:

0.000743

AC:

AN:

32286

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.417

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000372

AC:

AN:

147704

Hom.:

Cov.:

AF XY:

0.000431

AC XY:

AN XY:

71964

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40428

American (AMR)

AF:

0.0000677

AC:

AN:

14764

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3412

East Asian (EAS)

AF:

0.00

AC:

AN:

4958

South Asian (SAS)

AF:

0.00

AC:

AN:

4670

European-Finnish (FIN)

AF:

0.00381

AC:

AN:

9970

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.000241

AC:

AN:

66286

Other (OTH)

AF:

0.00

AC:

AN:

2042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000490

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Osteogenesis Imperfecta, Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.0070

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over