12-15484006-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_030667.3(PTPRO):c.108T>C(p.Asp36Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0292 in 1,613,578 control chromosomes in the GnomAD database, including 896 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 73 hom., cov: 32)

Exomes 𝑓: 0.030 ( 823 hom. )

Consequence

PTPRO
NM_030667.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.00100

Publications

4 publications found

Variant links:

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

PTPRO links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 12-15484006-T-C is Benign according to our data. Variant chr12-15484006-T-C is described in ClinVar as [Benign]. Clinvar id is 1234355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.001 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0248 (3771/152268) while in subpopulation NFE AF = 0.036 (2449/67970). AF 95% confidence interval is 0.0348. There are 73 homozygotes in GnomAd4. There are 1853 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 73 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRO	NM_030667.3 link	c.108T>C	p.Asp36Asp	synonymous_variant	Exon 2 of 27	ENST00000281171.9	NP_109592.1	Q16827-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRO	ENST00000281171.9 link	c.108T>C	p.Asp36Asp	synonymous_variant	Exon 2 of 27	1	NM_030667.3	ENSP00000281171.4		Q16827-1

Frequencies

GnomAD3 genomes

AF:

0.0248

AC:

3772

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00586

Gnomad AMI

AF:

0.152

Gnomad AMR

AF:

0.0151

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00517

Gnomad FIN

AF:

0.0558

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0360

Gnomad OTH

AF:

0.0229

GnomAD2 exomes

AF:

0.0237

AC:

5943

AN:

250984

AF XY:

0.0239

show subpopulations

Gnomad AFR exome

AF:

0.00474

Gnomad AMR exome

AF:

0.0121

Gnomad ASJ exome

AF:

0.0101

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0524

Gnomad NFE exome

AF:

0.0341

Gnomad OTH exome

AF:

0.0273

GnomAD4 exome

AF:

0.0297

AC:

43393

AN:

1461310

Hom.:

823

Cov.:

AF XY:

0.0291

AC XY:

21157

AN XY:

726976

show subpopulations

African (AFR)

AF:

0.00406

AC:

136

AN:

33466

American (AMR)

AF:

0.0127

AC:

570

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.0104

AC:

271

AN:

26124

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39682

South Asian (SAS)

AF:

0.00603

AC:

520

AN:

86244

European-Finnish (FIN)

AF:

0.0516

AC:

2756

AN:

53388

Middle Eastern (MID)

AF:

0.00641

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0337

AC:

37491

AN:

1111536

Other (OTH)

AF:

0.0266

AC:

1609

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

2229

4457

6686

8914

11143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0248

AC:

3771

AN:

152268

Hom.:

Cov.:

AF XY:

0.0249

AC XY:

1853

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.00584

AC:

243

AN:

41578

American (AMR)

AF:

0.0150

AC:

230

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0121

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00497

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0558

AC:

592

AN:

10614

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0360

AC:

2449

AN:

67970

Other (OTH)

AF:

0.0227

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

185

371

556

742

927

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0278

Hom.:

Bravo

AF:

0.0199

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.0316

EpiControl

AF:

0.0290

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 26, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 25, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

4.6

(source)

DANN

Benign

0.63

PhyloP100

0.0010

Mutation Taster

=93/7

polymorphism (auto)

(source)

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

Publications

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12-15484006-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over