NM_030667.3:c.2830-1367G>A

Variant names:

• chr12-15577486-G-A
• rs11056571
• NM_030667.3:c.2830-1367G>A

Variant summary

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

The NM_030667.3(PTPRO):​c.2830-1367G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,130 control chromosomes in the GnomAD database, including 2,886 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 0.19 (2886 hom., cov: 33)
• Consequence: PTPRO NM_030667.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.386
• Publications: 3 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030667.3. 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
	PTPRO	NM_030667.3	MANE Select	c.2830-1367G>A		intron	N/A	NP_109592.1	Q16827-1
	PTPRO	NM_002848.4		c.2746-1367G>A		intron	N/A	NP_002839.1	Q16827-2
	PTPRO	NM_030669.3		c.397-1367G>A		intron	N/A	NP_109594.1	Q16827-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRO	ENST00000281171.9	TSL:1 MANE Select	c.2830-1367G>A		intron	N/A	ENSP00000281171.4	Q16827-1
	PTPRO	ENST00000348962.7	TSL:1	c.2746-1367G>A		intron	N/A	ENSP00000343434.2	Q16827-2
	PTPRO	ENST00000442921.7	TSL:1	c.397-1367G>A		intron	N/A	ENSP00000404188.2	Q16827-3

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28846 AN: 152012 Hom.: 2890 Cov.: 33

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.190 AC: 28857 AN: 152130 Hom.: 2886 Cov.: 33 AF XY: 0.192 AC XY: 14246 AN XY: 74346

African (AFR) AF: 0.149 AC: 6190 AN: 41522

American (AMR) AF: 0.207 AC: 3157 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1007 AN: 3468

East Asian (EAS) AF: 0.258 AC: 1333 AN: 5172

South Asian (SAS) AF: 0.187 AC: 902 AN: 4822

European-Finnish (FIN) AF: 0.202 AC: 2138 AN: 10562

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.197 AC: 13426 AN: 67996

Other (OTH) AF: 0.222 AC: 468 AN: 2108

Alfa AF: 0.180 Hom.: 508

Bravo AF: 0.190

Asia WGS AF: 0.203 AC: 703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.9
DANN	Benign	0.49
PhyloP100		0.39
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: rs11056571; hg19: chr12-15730420;