rs17222089

Variant names:

• chr12-15573963-A-G
• rs17222089
• NM_030667.3:c.2829+4465A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-15573963-A-G
• chr12-15573963-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000281171.9(PTPRO):​c.2829+4465A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,192 control chromosomes in the GnomAD database, including 3,904 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (3904 hom., cov: 32)
• Consequence: PTPRO ENST00000281171.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.25
• Publications: 2 publications found

Genes affected

PTPRO (HGNC:9678): (protein tyrosine phosphatase receptor type O) This gene encodes a member of the R3 subtype family of receptor-type protein tyrosine phosphatases. These proteins are localized to the apical surface of polarized cells and may have tissue-specific functions through activation of Src family kinases. This gene contains two distinct promoters, and alternatively spliced transcript variants encoding multiple isoforms have been observed. The encoded proteins may have multiple isoform-specific and tissue-specific functions, including the regulation of osteoclast production and activity, inhibition of cell proliferation and facilitation of apoptosis. This gene is a candidate tumor suppressor, and decreased expression of this gene has been observed in several types of cancer. [provided by RefSeq, May 2011]

PTPRO Gene-Disease associations (from GenCC):

• nephrotic syndrome, type 6

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000281171.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRO	NM_030667.3	MANE Select	c.2829+4465A>G		intron	N/A	NP_109592.1
	PTPRO	NM_002848.4		c.2745+4465A>G		intron	N/A	NP_002839.1
	PTPRO	NM_030669.3		c.396+4465A>G		intron	N/A	NP_109594.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRO	ENST00000281171.9	TSL:1 MANE Select	c.2829+4465A>G		intron	N/A	ENSP00000281171.4
	PTPRO	ENST00000348962.7	TSL:1	c.2745+4465A>G		intron	N/A	ENSP00000343434.2
	PTPRO	ENST00000442921.7	TSL:1	c.396+4465A>G		intron	N/A	ENSP00000404188.2

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33657 AN: 152072 Hom.: 3905 Cov.: 32

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.245

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.221 AC: 33682 AN: 152192 Hom.: 3904 Cov.: 32 AF XY: 0.222 AC XY: 16530 AN XY: 74412

African (AFR) AF: 0.254 AC: 10550 AN: 41526

American (AMR) AF: 0.216 AC: 3306 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1006 AN: 3464

East Asian (EAS) AF: 0.297 AC: 1540 AN: 5184

South Asian (SAS) AF: 0.190 AC: 918 AN: 4820

European-Finnish (FIN) AF: 0.202 AC: 2145 AN: 10598

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13466 AN: 67992

Other (OTH) AF: 0.242 AC: 513 AN: 2116

Alfa AF: 0.202 Hom.: 550

Bravo AF: 0.226

Asia WGS AF: 0.224 AC: 778 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.19
DANN	Benign	0.46
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs17222089; hg19: chr12-15726897;