15-64155820-T-TA

Position:

• chr15-64155820-T-TA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

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

• Frequency:
  • Genomes: 𝑓 0.67 (35067 hom., cov: 0)
  • Exomes 𝑓: 0.48 (7945 hom.)
• Consequence: PPIB NM_000942.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B: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]

SNX22 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 15-64155820-T-TA is Benign according to our data. Variant chr15-64155820-T-TA is described in ClinVar as [Benign]. Clinvar id is 316696.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPIB	NM_000942.5	c.*202dupT		3_prime_UTR_variant	5/5	ENST00000300026.4	NP_000933.1
SNX22	NM_024798.3	c.*1325dupA		3_prime_UTR_variant	7/7	ENST00000325881.9	NP_079074.2
SNX22	XM_017022581.2	c.*1325dupA		3_prime_UTR_variant	6/6		XP_016878070.1
SNX22	NR_073534.2	n.1999dupA		non_coding_transcript_exon_variant	7/7

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.674 AC: 97050 AN: 143896 Hom.: 35067 Cov.: 0

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.771

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.907

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.686

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.680

GnomAD4 exome AF: 0.480 AC: 183480 AN: 382216 Hom.: 7945 Cov.: 7 AF XY: 0.475 AC XY: 95885 AN XY: 201918

Gnomad4 AFR exome AF: 0.387

Gnomad4 AMR exome AF: 0.494

Gnomad4 ASJ exome AF: 0.451

Gnomad4 EAS exome AF: 0.514

Gnomad4 SAS exome AF: 0.387

Gnomad4 FIN exome AF: 0.501

Gnomad4 NFE exome AF: 0.495

Gnomad4 OTH exome AF: 0.478

GnomAD4 genome AF: 0.674 AC: 97057 AN: 143916 Hom.: 35067 Cov.: 0 AF XY: 0.673 AC XY: 46808 AN XY: 69546

Gnomad4 AFR AF: 0.395

Gnomad4 AMR AF: 0.771

Gnomad4 ASJ AF: 0.628

Gnomad4 EAS AF: 0.907

Gnomad4 SAS AF: 0.431

Gnomad4 FIN AF: 0.810

Gnomad4 NFE AF: 0.802

Gnomad4 OTH AF: 0.683

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Osteogenesis Imperfecta, Recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs5813282; hg19: chr15-64448019;