Genetic Variant PTPRO:c.76-109A>G (chr12-15483865-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

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

The NM_030667.3(PTPRO):c.76-109A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000872 in 1,177,294 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0041 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00040 ( 1 hom. )

Consequence

PTPRO
NM_030667.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.11

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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 12-15483865-A-G is Benign according to our data. Variant chr12-15483865-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1315836.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRO	NM_030667.3 link	c.76-109A>G		intron_variant	Intron 1 of 26	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.76-109A>G		intron_variant	Intron 1 of 26	1	NM_030667.3	ENSP00000281171.4		Q16827-1

Frequencies

GnomAD3 genomes

AF:

0.00406

AC:

618

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0141

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00430

GnomAD4 exome

AF:

0.000399

AC:

409

AN:

1025024

Hom.:

AF XY:

0.000304

AC XY:

159

AN XY:

523376

show subpopulations

African (AFR)

AF:

0.0143

AC:

348

AN:

24280

American (AMR)

AF:

0.000610

AC:

AN:

37710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21892

East Asian (EAS)

AF:

0.00

AC:

AN:

37166

South Asian (SAS)

AF:

0.0000286

AC:

AN:

70036

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40820

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3528

European-Non Finnish (NFE)

AF:

0.00000403

AC:

AN:

743872

Other (OTH)

AF:

0.000722

AC:

AN:

45720

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00406

AC:

618

AN:

152270

Hom.:

Cov.:

AF XY:

0.00389

AC XY:

290

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0141

AC:

584

AN:

41562

American (AMR)

AF:

0.00144

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

67988

Other (OTH)

AF:

0.00426

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

118

147

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000698

Hom.:

Bravo

AF:

0.00457

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 03, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.87

(source)

DANN

Benign

0.77

PhyloP100

-1.1

Mutation Taster

=100/0

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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12-15483865-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over