12-15407262-A-G

Variant names:

• chr12-15407262-A-G
• rs4764191
• NM_030667.3:c.76-76712A>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.76-76712A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.847 in 152,180 control chromosomes in the GnomAD database, including 56,085 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 0.85 (56085 hom., cov: 32)
• Consequence: PTPRO NM_030667.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.178
• 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: 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 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.76-76712A>G		intron	N/A	NP_109592.1	Q16827-1
	PTPRO	NM_002848.4		c.76-76712A>G		intron	N/A	NP_002839.1	Q16827-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRO	ENST00000281171.9	TSL:1 MANE Select	c.76-76712A>G		intron	N/A	ENSP00000281171.4	Q16827-1
	PTPRO	ENST00000348962.7	TSL:1	c.76-76712A>G		intron	N/A	ENSP00000343434.2	Q16827-2
	PTPRO	ENST00000543886.6	TSL:1	c.76-76712A>G		intron	N/A	ENSP00000444173.1	Q16827-5

Frequencies

GnomAD3 genomes AF: 0.847 AC: 128846 AN: 152062 Hom.: 56068 Cov.: 32

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.928

Gnomad AMR AF: 0.917

Gnomad ASJ AF: 0.901

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.938

Gnomad FIN AF: 0.947

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.930

Gnomad OTH AF: 0.880

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

GnomAD4 genome AF: 0.847 AC: 128907 AN: 152180 Hom.: 56085 Cov.: 32 AF XY: 0.852 AC XY: 63379 AN XY: 74420

African (AFR) AF: 0.627 AC: 25998 AN: 41470

American (AMR) AF: 0.917 AC: 14004 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.901 AC: 3128 AN: 3472

East Asian (EAS) AF: 0.956 AC: 4960 AN: 5186

South Asian (SAS) AF: 0.938 AC: 4523 AN: 4820

European-Finnish (FIN) AF: 0.947 AC: 10050 AN: 10616

Middle Eastern (MID) AF: 0.929 AC: 273 AN: 294

European-Non Finnish (NFE) AF: 0.930 AC: 63263 AN: 68020

Other (OTH) AF: 0.880 AC: 1862 AN: 2116

Alfa AF: 0.909 Hom.: 105831

Bravo AF: 0.834

Asia WGS AF: 0.919 AC: 3196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.2
DANN	Benign	0.82
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: rs4764191; hg19: chr12-15560196;