15-64155820-T-TAA

Position:

• chr15-64155820-T-TAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000942.5(PPIB):​c.*201_*202dupTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.046 (155 hom., cov: 0)
  • Exomes 𝑓: 0.17 (45 hom.)
• Consequence: PPIB NM_000942.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: -0.0930

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

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPIB	NM_000942.5	c.*201_*202dupTT		3_prime_UTR_variant	5/5	ENST00000300026.4	NP_000933.1
SNX22	NM_024798.3	c.*1324_*1325dupAA		3_prime_UTR_variant	7/7	ENST00000325881.9	NP_079074.2
SNX22	XM_017022581.2	c.*1324_*1325dupAA		3_prime_UTR_variant	6/6		XP_016878070.1
SNX22	NR_073534.2	n.1998_1999dupAA		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPIB	ENST00000300026	c.*201_*202dupTT		3_prime_UTR_variant	5/5	1	NM_000942.5	ENSP00000300026.4
SNX22	ENST00000325881.9	c.*1324_*1325dupAA		3_prime_UTR_variant	7/7	1	NM_024798.3	ENSP00000323435.4

Frequencies

GnomAD3 genomes AF: 0.0460 AC: 6622 AN: 143866 Hom.: 156 Cov.: 0

Gnomad AFR AF: 0.0271

Gnomad AMI AF: 0.0850

Gnomad AMR AF: 0.0667

Gnomad ASJ AF: 0.0301

Gnomad EAS AF: 0.0458

Gnomad SAS AF: 0.0747

Gnomad FIN AF: 0.0521

Gnomad MID AF: 0.0658

Gnomad NFE AF: 0.0498

Gnomad OTH AF: 0.0577

GnomAD4 exome AF: 0.173 AC: 62042 AN: 359554 Hom.: 45 Cov.: 7 AF XY: 0.170 AC XY: 32500 AN XY: 190992

Gnomad4 AFR exome AF: 0.0557

Gnomad4 AMR exome AF: 0.189

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.235

Gnomad4 SAS exome AF: 0.117

Gnomad4 FIN exome AF: 0.190

Gnomad4 NFE exome AF: 0.184

Gnomad4 OTH exome AF: 0.166

GnomAD4 genome AF: 0.0461 AC: 6626 AN: 143886 Hom.: 155 Cov.: 0 AF XY: 0.0469 AC XY: 3260 AN XY: 69530

Gnomad4 AFR AF: 0.0273

Gnomad4 AMR AF: 0.0668

Gnomad4 ASJ AF: 0.0301

Gnomad4 EAS AF: 0.0456

Gnomad4 SAS AF: 0.0753

Gnomad4 FIN AF: 0.0521

Gnomad4 NFE AF: 0.0498

Gnomad4 OTH AF: 0.0578

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Osteogenesis Imperfecta, Recessive Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs5813282; hg19: chr15-64448019;