12-15463610-A-G

Variant names:

• chr12-15463610-A-G
• rs253810
• NM_030667.3:c.76-20364A>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.76-20364A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.92 in 152,166 control chromosomes in the GnomAD database, including 65,213 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 0.92 (65213 hom., cov: 31)
• Consequence: PTPRO NM_030667.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.181
• Publications: 1 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.985 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.76-20364A>G		intron	N/A	NP_109592.1
	PTPRO	NM_002848.4		c.76-20364A>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.76-20364A>G		intron	N/A	ENSP00000281171.4
	PTPRO	ENST00000348962.7	TSL:1	c.76-20364A>G		intron	N/A	ENSP00000343434.2
	PTPRO	ENST00000543886.6	TSL:1	c.76-20364A>G		intron	N/A	ENSP00000444173.1

Frequencies

GnomAD3 genomes AF: 0.920 AC: 139925 AN: 152048 Hom.: 65177 Cov.: 31

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.961

Gnomad ASJ AF: 0.988

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.977

Gnomad FIN AF: 0.999

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.992

Gnomad OTH AF: 0.932

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

GnomAD4 genome AF: 0.920 AC: 140019 AN: 152166 Hom.: 65213 Cov.: 31 AF XY: 0.922 AC XY: 68591 AN XY: 74388

African (AFR) AF: 0.761 AC: 31559 AN: 41468

American (AMR) AF: 0.961 AC: 14692 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.988 AC: 3428 AN: 3470

East Asian (EAS) AF: 0.858 AC: 4440 AN: 5174

South Asian (SAS) AF: 0.977 AC: 4707 AN: 4818

European-Finnish (FIN) AF: 0.999 AC: 10603 AN: 10616

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.992 AC: 67436 AN: 68012

Other (OTH) AF: 0.931 AC: 1965 AN: 2110

Alfa AF: 0.954 Hom.: 10174

Bravo AF: 0.910

Asia WGS AF: 0.906 AC: 3148 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.59
PhyloP100		0.18
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: rs253810; hg19: chr12-15616544;