rs1143699

Positions:

• chr19-5210751-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002850.4(PTPRS):​c.5289C>T​(p.Asp1763=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0999 in 1,614,040 control chromosomes in the GnomAD database, including 9,106 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1285 hom., cov: 33)
  • Exomes 𝑓: 0.098 (7821 hom.)
• Consequence: PTPRS NM_002850.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.528

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=0.528 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRS	NM_002850.4	c.5289C>T	p.Asp1763=	synonymous_variant	34/38	ENST00000262963.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRS	ENST00000262963.11	c.5289C>T	p.Asp1763=	synonymous_variant	34/38	5	NM_002850.4	A1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18197 AN: 152162 Hom.: 1282 Cov.: 33

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.0846

Gnomad AMR AF: 0.0824

Gnomad ASJ AF: 0.0832

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0507

Gnomad FIN AF: 0.0819

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.113

GnomAD3 exomes AF: 0.0876 AC: 21998 AN: 251126 Hom.: 1293 AF XY: 0.0859 AC XY: 11664 AN XY: 135820

Gnomad AFR exome AF: 0.197

Gnomad AMR exome AF: 0.0495

Gnomad ASJ exome AF: 0.0893

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.0511

Gnomad FIN exome AF: 0.0830

Gnomad NFE exome AF: 0.108

Gnomad OTH exome AF: 0.0858

GnomAD4 exome AF: 0.0979 AC: 143108 AN: 1461760 Hom.: 7821 Cov.: 34 AF XY: 0.0957 AC XY: 69565 AN XY: 727188

Gnomad4 AFR exome AF: 0.197

Gnomad4 AMR exome AF: 0.0530

Gnomad4 ASJ exome AF: 0.0895

Gnomad4 EAS exome AF: 0.000277

Gnomad4 SAS exome AF: 0.0494

Gnomad4 FIN exome AF: 0.0823

Gnomad4 NFE exome AF: 0.105

Gnomad4 OTH exome AF: 0.0965

GnomAD4 genome AF: 0.120 AC: 18206 AN: 152280 Hom.: 1285 Cov.: 33 AF XY: 0.116 AC XY: 8659 AN XY: 74470

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.0822

Gnomad4 ASJ AF: 0.0832

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0501

Gnomad4 FIN AF: 0.0819

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.112

Alfa AF: 0.102 Hom.: 1848

Bravo AF: 0.122

Asia WGS AF: 0.0430 AC: 152 AN: 3478

EpiCase AF: 0.0995

EpiControl AF: 0.100

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	1.3
DANN	Benign	0.68

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: rs1143699; hg19: chr19-5210762;