Variant 19-5273560-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002850.4(PTPRS):c.261A>C(p.Ala87Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,613,918 control chromosomes in the GnomAD database, including 37,869 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 3953 hom., cov: 32)

Exomes 𝑓: 0.21 ( 33916 hom. )

Consequence

PTPRS
NM_002850.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -4.08

Variant links:

Genes affected

PTPRS (HGNC:9681): (protein tyrosine phosphatase receptor type S) 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 contains an extracellular region, a single transmembrane segment and two tandem intracytoplasmic catalytic domains, and thus represents a receptor-type PTP. The extracellular region of this protein is composed of multiple Ig-like and fibronectin type III-like domains. Studies of the similar gene in mice suggested that this PTP may be involved in cell-cell interaction, primary axonogenesis, and axon guidance during embryogenesis. This PTP has been also implicated in the molecular control of adult nerve repair. Four alternatively spliced transcript variants, which encode distinct proteins, have been reported. [provided by RefSeq, Jul 2008]

PTPRS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 19-5273560-T-G is Benign according to our data. Variant chr19-5273560-T-G is described in ClinVar as [Benign]. Clinvar id is 1263463.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.09 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRS	NM_002850.4 link	c.261A>C	p.Ala87Ala	synonymous_variant	4/38	ENST00000262963.11	NP_002841.3	Q13332-1Q8NHS7Q59FX6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRS	ENST00000262963.11 link	c.261A>C	p.Ala87Ala	synonymous_variant	4/38	5	NM_002850.4	ENSP00000262963.8		Q13332-1G8JL96

Frequencies

GnomAD3 genomes

AF:

0.216

AC:

32804

AN:

151990

Hom.:

3947

Cov.:

show subpopulations

Gnomad AFR

AF:

0.266

Gnomad AMI

AF:

0.169

Gnomad AMR

AF:

0.174

Gnomad ASJ

AF:

0.318

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.125

Gnomad FIN

AF:

0.138

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.224

Gnomad OTH

AF:

0.243

GnomAD3 exomes

AF:

0.182

AC:

45793

AN:

251308

Hom.:

5033

AF XY:

0.185

AC XY:

25063

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.263

Gnomad AMR exome

AF:

0.119

Gnomad ASJ exome

AF:

0.321

Gnomad EAS exome

AF:

0.000816

Gnomad SAS exome

AF:

0.125

Gnomad FIN exome

AF:

0.148

Gnomad NFE exome

AF:

0.227

Gnomad OTH exome

AF:

0.209

GnomAD4 exome

AF:

0.208

AC:

303685

AN:

1461810

Hom.:

33916

Cov.:

AF XY:

0.207

AC XY:

150180

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.264

Gnomad4 AMR exome

AF:

0.128

Gnomad4 ASJ exome

AF:

0.323

Gnomad4 EAS exome

AF:

0.000705

Gnomad4 SAS exome

AF:

0.130

Gnomad4 FIN exome

AF:

0.153

Gnomad4 NFE exome

AF:

0.222

Gnomad4 OTH exome

AF:

0.211

GnomAD4 genome

AF:

0.216

AC:

32817

AN:

152108

Hom.:

3953

Cov.:

AF XY:

0.206

AC XY:

15291

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.266

Gnomad4 AMR

AF:

0.173

Gnomad4 ASJ

AF:

0.318

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.126

Gnomad4 FIN

AF:

0.138

Gnomad4 NFE

AF:

0.224

Gnomad4 OTH

AF:

0.240

Alfa

AF:

0.221

Hom.:

6369

Bravo

AF:

0.220

EpiCase

AF:

0.241

EpiControl

AF:

0.240

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 27, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.028

DANN

Benign

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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