NM_030667.3:c.76-27831C>T

Variant names:

• chr12-15456143-C-T
• rs11056500
• NM_030667.3:c.76-27831C>T

Variant summary

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

The NM_030667.3(PTPRO):​c.76-27831C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 151,978 control chromosomes in the GnomAD database, including 2,845 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 (2845 hom., cov: 33)
• Consequence: PTPRO NM_030667.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.251
• Publications: 7 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.313 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.76-27831C>T		intron	N/A	NP_109592.1
	PTPRO	NM_002848.4		c.76-27831C>T		intron	N/A	NP_002839.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRO	ENST00000281171.9	TSL:1 MANE Select	c.76-27831C>T		intron	N/A	ENSP00000281171.4
	PTPRO	ENST00000348962.7	TSL:1	c.76-27831C>T		intron	N/A	ENSP00000343434.2
	PTPRO	ENST00000543886.6	TSL:1	c.76-27831C>T		intron	N/A	ENSP00000444173.1

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28737 AN: 151862 Hom.: 2846 Cov.: 33

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.189 AC: 28743 AN: 151978 Hom.: 2845 Cov.: 33 AF XY: 0.192 AC XY: 14298 AN XY: 74284

African (AFR) AF: 0.140 AC: 5808 AN: 41474

American (AMR) AF: 0.176 AC: 2694 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 815 AN: 3466

East Asian (EAS) AF: 0.326 AC: 1685 AN: 5172

South Asian (SAS) AF: 0.166 AC: 800 AN: 4814

European-Finnish (FIN) AF: 0.215 AC: 2265 AN: 10532

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14073 AN: 67938

Other (OTH) AF: 0.197 AC: 416 AN: 2110

Alfa AF: 0.200 Hom.: 2915

Bravo AF: 0.184

Asia WGS AF: 0.225 AC: 781 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	7.4
DANN	Benign	0.28
PhyloP100		0.25
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: rs11056500; hg19: chr12-15609077;