Variant 12-15484006-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_030667.3(PTPRO):c.108T>C(p.Asp36=) 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

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 made for transcript

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 73 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRO	NM_030667.3 linkuse as main transcript	c.108T>C	p.Asp36=	synonymous_variant	2/27	ENST00000281171.9	NP_109592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRO	ENST00000281171.9 linkuse as main transcript	c.108T>C	p.Asp36=	synonymous_variant	2/27	1	NM_030667.3	ENSP00000281171	P4	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

GnomAD3 exomes

AF:

0.0237

AC:

5943

AN:

250984

Hom.:

103

AF XY:

0.0239

AC XY:

3237

AN XY:

135676

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 SAS exome

AF:

0.00595

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

Gnomad4 AFR exome

AF:

0.00406

Gnomad4 AMR exome

AF:

0.0127

Gnomad4 ASJ exome

AF:

0.0104

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00603

Gnomad4 FIN exome

AF:

0.0516

Gnomad4 NFE exome

AF:

0.0337

Gnomad4 OTH exome

AF:

0.0266

GnomAD4 genome

AF:

0.0248

AC:

3771

AN:

152268

Hom.:

Cov.:

AF XY:

0.0249

AC XY:

1853

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00584

Gnomad4 AMR

AF:

0.0150

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00497

Gnomad4 FIN

AF:

0.0558

Gnomad4 NFE

AF:

0.0360

Gnomad4 OTH

AF:

0.0227

Alfa

AF:

0.0287

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 25, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

4.6

DANN

Benign

0.63

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over