NM_030667.3:c.31G>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_030667.3(PTPRO):c.31G>T(p.Ala11Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00105 in 1,611,168 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A11T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00083 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 6 hom. )

Consequence

PTPRO
NM_030667.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -1.13

Publications

2 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 links:

RERG (HGNC:15980): (RAS like estrogen regulated growth inhibitor) RERG, a member of the RAS superfamily of GTPases, inhibits cell proliferation and tumor formation (Finlin et al., 2001 [PubMed 11533059]).[supplied by OMIM, Mar 2009]

RERG links:

LOC105369673 (HGNC:):

LOC105369673 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035243034).

BP6

Variant 12-15322757-G-T is Benign according to our data. Variant chr12-15322757-G-T is described in ClinVar as Benign. ClinVar VariationId is 1614800.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 AR,AD gene

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.31G>T	p.Ala11Ser	missense	Exon 1 of 27	NP_109592.1	Q16827-1
	PTPRO	NM_002848.4		c.31G>T	p.Ala11Ser	missense	Exon 1 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.31G>T	p.Ala11Ser	missense	Exon 1 of 27	ENSP00000281171.4	Q16827-1
PTPRO	ENST00000348962.7	TSL:1	c.31G>T	p.Ala11Ser	missense	Exon 1 of 26	ENSP00000343434.2	Q16827-2
PTPRO	ENST00000543886.6	TSL:1	c.31G>T	p.Ala11Ser	missense	Exon 1 of 9	ENSP00000444173.1	Q16827-5

Frequencies

GnomAD3 genomes

AF:

0.000834

AC:

127

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00126

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000814

AC:

196

AN:

240906

AF XY:

0.000926

show subpopulations

Gnomad AFR exome

AF:

0.000131

Gnomad AMR exome

AF:

0.000321

Gnomad ASJ exome

AF:

0.00617

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000197

Gnomad NFE exome

AF:

0.00103

Gnomad OTH exome

AF:

0.00102

GnomAD4 exome

AF:

0.00107

AC:

1567

AN:

1458870

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

765

AN XY:

725696

show subpopulations

African (AFR)

AF:

0.000180

AC:

AN:

33394

American (AMR)

AF:

0.000269

AC:

AN:

44652

Ashkenazi Jewish (ASJ)

AF:

0.00756

AC:

197

AN:

26062

East Asian (EAS)

AF:

0.00

AC:

AN:

39640

South Asian (SAS)

AF:

0.0000814

AC:

AN:

86020

European-Finnish (FIN)

AF:

0.000114

AC:

AN:

52796

Middle Eastern (MID)

AF:

0.000202

AC:

AN:

4962

European-Non Finnish (NFE)

AF:

0.00112

AC:

1241

AN:

1111228

Other (OTH)

AF:

0.00161

AC:

AN:

60116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

170

255

340

425

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<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

AF:

0.000834

AC:

127

AN:

152298

Hom.:

Cov.:

AF XY:

0.000685

AC XY:

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.000192

AC:

AN:

41578

American (AMR)

AF:

0.000261

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00749

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000282

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00126

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00132

Hom.:

Bravo

AF:

0.000805

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.000719

AC:

EpiCase

AF:

0.000763

EpiControl

AF:

0.00154

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

PTPRO-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.9

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.092

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.57

M_CAP

Benign

0.016

MetaRNN

Benign

0.0035

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.34

PhyloP100

-1.1

PrimateAI

Benign

0.44

PROVEAN

Benign

0.30

REVEL

Benign

0.027

Sift

Uncertain

0.011

Sift4G

Benign

0.076

Polyphen

0.0

Vest4

0.044

MVP

0.14

MPC

0.25

ClinPred

0.0032

GERP RS

-2.1

PromoterAI

-0.0096

Neutral

(source)

Varity_R

0.11

gMVP

0.29

Mutation Taster

=99/1

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over