Variant chr1-43569681-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The NM_002840.5(PTPRF):c.471C>T(p.Ala157Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 1,613,450 control chromosomes in the GnomAD database, including 74,235 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.24 ( 5339 hom., cov: 33)

Exomes 𝑓: 0.30 ( 68896 hom. )

Consequence

PTPRF
NM_002840.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.18

Variant links:

Genes affected

PTPRF (HGNC:9670): (protein tyrosine phosphatase receptor type F) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP possesses an extracellular region, a single transmembrane region, and two tandem intracytoplasmic catalytic domains, and thus represents a receptor-type PTP. The extracellular region contains three Ig-like domains, and nine non-Ig like domains similar to that of neural-cell adhesion molecule. This PTP was shown to function in the regulation of epithelial cell-cell contacts at adherents junctions, as well as in the control of beta-catenin signaling. An increased expression level of this protein was found in the insulin-responsive tissue of obese, insulin-resistant individuals, and may contribute to the pathogenesis of insulin resistance. Two alternatively spliced transcript variants of this gene, which encode distinct proteins, have been reported. [provided by RefSeq, Jul 2008]

PTPRF links:

PTPRF (HGNC:):

PTPRF links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 1-43569681-C-T is Benign according to our data. Variant chr1-43569681-C-T is described in ClinVar as [Benign]. Clinvar id is 3059678.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-2.18 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRF	NM_002840.5 linkuse as main transcript	c.471C>T	p.Ala157Ala	synonymous_variant	6/34	ENST00000359947.9	NP_002831.2	P10586-1G1UI20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRF	ENST00000359947.9 linkuse as main transcript	c.471C>T	p.Ala157Ala	synonymous_variant	6/34	1	NM_002840.5	ENSP00000353030.4		P10586-1

Frequencies

GnomAD3 genomes

AF:

0.241

AC:

36599

AN:

151994

Hom.:

5337

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0699

Gnomad AMI

AF:

0.230

Gnomad AMR

AF:

0.237

Gnomad ASJ

AF:

0.270

Gnomad EAS

AF:

0.325

Gnomad SAS

AF:

0.276

Gnomad FIN

AF:

0.352

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.319

Gnomad OTH

AF:

0.235

GnomAD3 exomes

AF:

0.286

AC:

71865

AN:

251022

Hom.:

10980

AF XY:

0.289

AC XY:

39213

AN XY:

135658

show subpopulations

Gnomad AFR exome

AF:

0.0687

Gnomad AMR exome

AF:

0.264

Gnomad ASJ exome

AF:

0.273

Gnomad EAS exome

AF:

0.342

Gnomad SAS exome

AF:

0.270

Gnomad FIN exome

AF:

0.346

Gnomad NFE exome

AF:

0.309

Gnomad OTH exome

AF:

0.293

GnomAD4 exome

AF:

0.303

AC:

442799

AN:

1461338

Hom.:

68896

Cov.:

AF XY:

0.303

AC XY:

220027

AN XY:

726960

show subpopulations

Gnomad4 AFR exome

AF:

0.0599

Gnomad4 AMR exome

AF:

0.261

Gnomad4 ASJ exome

AF:

0.276

Gnomad4 EAS exome

AF:

0.303

Gnomad4 SAS exome

AF:

0.269

Gnomad4 FIN exome

AF:

0.343

Gnomad4 NFE exome

AF:

0.315

Gnomad4 OTH exome

AF:

0.290

GnomAD4 genome

AF:

0.241

AC:

36616

AN:

152112

Hom.:

5339

Cov.:

AF XY:

0.242

AC XY:

17985

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0700

Gnomad4 AMR

AF:

0.237

Gnomad4 ASJ

AF:

0.270

Gnomad4 EAS

AF:

0.325

Gnomad4 SAS

AF:

0.275

Gnomad4 FIN

AF:

0.352

Gnomad4 NFE

AF:

0.319

Gnomad4 OTH

AF:

0.238

Alfa

AF:

0.296

Hom.:

13925

Bravo

AF:

0.226

Asia WGS

AF:

0.308

AC:

1071

AN:

3478

EpiCase

AF:

0.305

EpiControl

AF:

0.293

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PTPRF-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

1.1

DANN

Benign

0.49

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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