chr15-64155833-AC-A

Variant names:

• chr15-64155833-AC-A
• rs397748288
• NM_000942.5:c.*189delG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000942.5(PPIB):​c.*189delG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000155 in 645,032 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: PPIB NM_000942.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700
• Publications: 0 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]

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.*189delG		3_prime_UTR	Exon 5 of 5	NP_000933.1	P23284
	SNX22	NM_024798.3	MANE Select	c.*1328delC		3_prime_UTR	Exon 7 of 7	NP_079074.2	Q96L94-1
	SNX22	NR_073534.2		n.2002delC		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000155 AC: 1 AN: 645032 Hom.: 0 Cov.: 8 AF XY: 0.00000298 AC XY: 1 AN XY: 335316

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 15384

American (AMR) AF: 0.00 AC: 0 AN: 20292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16508

East Asian (EAS) AF: 0.00 AC: 0 AN: 31086

South Asian (SAS) AF: 0.0000184 AC: 1 AN: 54248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30328

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2414

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 442484

Other (OTH) AF: 0.00 AC: 0 AN: 32288

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

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

Other links and lift over

dbSNP: rs397748288; hg19: chr15-64448032;