Variant 20-42084674-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_007050.6(PTPRT):c.4136+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0374 in 1,484,716 control chromosomes in the GnomAD database, including 1,208 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.029 ( 89 hom., cov: 32)

Exomes 𝑓: 0.038 ( 1119 hom. )

Consequence

PTPRT
NM_007050.6 splice_region, intron

Scores

Splicing: ADA: 0.0003574

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.433

Variant links:

Genes affected

PTPRT (HGNC:9682): (protein tyrosine phosphatase receptor type T) 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 intracellular catalytic domains, and thus represents a receptor-type PTP. The extracellular region contains a meprin-A5 antigen-PTP (MAM) domain, Ig-like and fibronectin type III-like repeats. The protein domain structure and the expression pattern of the mouse counterpart of this PTP suggest its roles in both signal transduction and cellular adhesion in the central nervous system. Two alternatively spliced transcript variants of this gene, which encode distinct proteins, have been reported. [provided by RefSeq, Jul 2008]

PTPRT links:

LOC101927182 (HGNC:):

LOC101927182 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 20-42084674-G-A is Benign according to our data. Variant chr20-42084674-G-A is described in ClinVar as [Benign]. Clinvar id is 3056155.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRT	NM_007050.6 linkuse as main transcript	c.4136+8C>T		splice_region_variant, intron_variant		ENST00000373187.6	NP_008981.4	O14522-3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
PTPRT	ENST00000373187.6 linkuse as main transcript	c.4136+8C>T	splice_region_variant, intron_variant	1	NM_007050.6	ENSP00000362283.1	O14522-3
PTPRT	ENST00000373193.7 linkuse as main transcript	c.4202+8C>T	splice_region_variant, intron_variant	1		ENSP00000362289.4	O14522-1
PTPRT	ENST00000617474.1 linkuse as main transcript	n.*4003+8C>T	splice_region_variant, intron_variant	5		ENSP00000484248.1	A0A087X1J1

Frequencies

GnomAD3 genomes

AF:

0.0286

AC:

4351

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00734

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.0298

Gnomad ASJ

AF:

0.0311

Gnomad EAS

AF:

0.101

Gnomad SAS

AF:

0.0522

Gnomad FIN

AF:

0.0214

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0356

Gnomad OTH

AF:

0.0272

GnomAD3 exomes

AF:

0.0389

AC:

7626

AN:

196174

Hom.:

215

AF XY:

0.0380

AC XY:

3993

AN XY:

104968

show subpopulations

Gnomad AFR exome

AF:

0.00706

Gnomad AMR exome

AF:

0.0522

Gnomad ASJ exome

AF:

0.0335

Gnomad EAS exome

AF:

0.0942

Gnomad SAS exome

AF:

0.0468

Gnomad FIN exome

AF:

0.0200

Gnomad NFE exome

AF:

0.0339

Gnomad OTH exome

AF:

0.0357

GnomAD4 exome

AF:

0.0384

AC:

51143

AN:

1332456

Hom.:

1119

Cov.:

AF XY:

0.0382

AC XY:

24944

AN XY:

653658

show subpopulations

Gnomad4 AFR exome

AF:

0.00656

Gnomad4 AMR exome

AF:

0.0473

Gnomad4 ASJ exome

AF:

0.0305

Gnomad4 EAS exome

AF:

0.0837

Gnomad4 SAS exome

AF:

0.0445

Gnomad4 FIN exome

AF:

0.0219

Gnomad4 NFE exome

AF:

0.0381

Gnomad4 OTH exome

AF:

0.0385

GnomAD4 genome

AF:

0.0286

AC:

4352

AN:

152260

Hom.:

Cov.:

AF XY:

0.0286

AC XY:

2128

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00732

Gnomad4 AMR

AF:

0.0300

Gnomad4 ASJ

AF:

0.0311

Gnomad4 EAS

AF:

0.101

Gnomad4 SAS

AF:

0.0520

Gnomad4 FIN

AF:

0.0214

Gnomad4 NFE

AF:

0.0356

Gnomad4 OTH

AF:

0.0269

Alfa

AF:

0.0330

Hom.:

Bravo

AF:

0.0278

Asia WGS

AF:

0.0860

AC:

297

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PTPRT-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 23, 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

-0.71

CADD

Benign

4.9

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00036

dbscSNV1_RF

Benign

0.018

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