12-15508036-A-G

Variant names:

• chr12-15508036-A-G
• rs1861594
• NM_030667.3:c.1268-535A>G

Variant summary

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

The NM_030667.3(PTPRO):​c.1268-535A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 151,886 control chromosomes in the GnomAD database, including 18,251 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 0.48 (18251 hom., cov: 32)
• Consequence: PTPRO NM_030667.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.257
• Publications: 5 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.59 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRO	NM_030667.3	MANE Select	c.1268-535A>G		intron	N/A	NP_109592.1
	PTPRO	NM_002848.4		c.1268-535A>G		intron	N/A	NP_002839.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRO	ENST00000281171.9	TSL:1 MANE Select	c.1268-535A>G		intron	N/A	ENSP00000281171.4
	PTPRO	ENST00000348962.7	TSL:1	c.1268-535A>G		intron	N/A	ENSP00000343434.2
	PTPRO	ENST00000543886.6	TSL:1	c.1268-535A>G		intron	N/A	ENSP00000444173.1

Frequencies

GnomAD3 genomes AF: 0.481 AC: 72951 AN: 151768 Hom.: 18224 Cov.: 32

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.481 AC: 73027 AN: 151886 Hom.: 18251 Cov.: 32 AF XY: 0.475 AC XY: 35221 AN XY: 74216

African (AFR) AF: 0.596 AC: 24660 AN: 41394

American (AMR) AF: 0.544 AC: 8299 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1563 AN: 3468

East Asian (EAS) AF: 0.163 AC: 843 AN: 5164

South Asian (SAS) AF: 0.376 AC: 1810 AN: 4814

European-Finnish (FIN) AF: 0.429 AC: 4513 AN: 10530

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.440 AC: 29883 AN: 67946

Other (OTH) AF: 0.452 AC: 954 AN: 2110

Alfa AF: 0.457 Hom.: 23658

Bravo AF: 0.499

Asia WGS AF: 0.293 AC: 1023 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.6
DANN	Benign	0.75
PhyloP100		0.26
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: rs1861594; hg19: chr12-15660970;