12-15484043-G-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030667.3(PTPRO):c.145G>C(p.Val49Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V49I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PTPRO
NM_030667.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.424

Publications

1 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11403045).

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.145G>C	p.Val49Leu	missense	Exon 2 of 27	NP_109592.1	Q16827-1
	PTPRO	NM_002848.4		c.145G>C	p.Val49Leu	missense	Exon 2 of 26	NP_002839.1	Q16827-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTPRO	ENST00000281171.9	TSL:1 MANE Select	c.145G>C	p.Val49Leu	missense	Exon 2 of 27	ENSP00000281171.4	Q16827-1
PTPRO	ENST00000348962.7	TSL:1	c.145G>C	p.Val49Leu	missense	Exon 2 of 26	ENSP00000343434.2	Q16827-2
PTPRO	ENST00000543886.6	TSL:1	c.145G>C	p.Val49Leu	missense	Exon 2 of 9	ENSP00000444173.1	Q16827-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251062

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461416

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727060

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33460

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111634

Other (OTH)

AF:

0.00

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.054

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.13

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.86

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.75

M_CAP

Benign

0.0090

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.69

PhyloP100

0.42

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.95

REVEL

Benign

0.029

Sift

Benign

0.33

Sift4G

Benign

0.47

Polyphen

0.0

Vest4

0.36

MutPred

0.27

Gain of catalytic residue at E45 (P = 0.0028)

MVP

0.16

MPC

0.27

ClinPred

0.046

GERP RS

0.50

Varity_R

0.053

gMVP

0.19

Mutation Taster

=79/21

polymorphism

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over