19-5211601-A-G

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_002850.4(PTPRS):c.5223T>C(p.Ile1741=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 1,608,126 control chromosomes in the GnomAD database, including 142 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0075 (9 hom., cov: 33)
  • Exomes 𝑓: 0.011 (133 hom.)
• Consequence: PTPRS NM_002850.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.272

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]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 19-5211601-A-G is Benign according to our data. Variant chr19-5211601-A-G is described in ClinVar as [Benign]. Clinvar id is 782049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.272 with no splicing effect.
• BS2: High AC in GnomAd at 1141 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRS	NM_002850.4	c.5223T>C	p.Ile1741=	synonymous_variant	33/38	ENST00000262963.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRS	ENST00000262963.11	c.5223T>C	p.Ile1741=	synonymous_variant	33/38	5	NM_002850.4	A1

Frequencies

GnomAD3 genomes AF: 0.00750 AC: 1141 AN: 152200 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.00212

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.0121

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0113

Gnomad OTH AF: 0.00765

GnomAD3 exomes AF: 0.00817 AC: 2050 AN: 250954 Hom.: 17 AF XY: 0.00849 AC XY: 1152 AN XY: 135660

Gnomad AFR exome AF: 0.00154

Gnomad AMR exome AF: 0.00278

Gnomad ASJ exome AF: 0.0210

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00395

Gnomad FIN exome AF: 0.0125

Gnomad NFE exome AF: 0.0113

Gnomad OTH exome AF: 0.00801

GnomAD4 exome AF: 0.0111 AC: 16211 AN: 1455808 Hom.: 133 Cov.: 33 AF XY: 0.0108 AC XY: 7832 AN XY: 722804

Gnomad4 AFR exome AF: 0.00147

Gnomad4 AMR exome AF: 0.00280

Gnomad4 ASJ exome AF: 0.0214

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00404

Gnomad4 FIN exome AF: 0.0134

Gnomad4 NFE exome AF: 0.0125

Gnomad4 OTH exome AF: 0.00924

GnomAD4 genome AF: 0.00748 AC: 1140 AN: 152318 Hom.: 9 Cov.: 33 AF XY: 0.00726 AC XY: 541 AN XY: 74480

Gnomad4 AFR AF: 0.00212

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.0251

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00352

Gnomad4 FIN AF: 0.0121

Gnomad4 NFE AF: 0.0113

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.0107 Hom.: 3

Bravo AF: 0.00644

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.0104

EpiControl AF: 0.0104

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2022	PTPRS: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

PTPRS-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 07, 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	-0.61
Cadd	Benign	4.0
Dann	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs41276864; hg19: chr19-5211612; COSMIC: COSV99508547; COSMIC: COSV99508547;