rs3746130

Positions:

• chr19-5240381-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002850.4(PTPRS):​c.1571-49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,507,294 control chromosomes in the GnomAD database, including 19,373 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 0.11 (1830 hom., cov: 31)
  • Exomes 𝑓: 0.13 (17543 hom.)
• Consequence: PTPRS NM_002850.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0510

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRS	NM_002850.4	c.1571-49G>A		intron_variant		ENST00000262963.11	NP_002841.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRS	ENST00000262963.11	c.1571-49G>A		intron_variant		5	NM_002850.4	ENSP00000262963	A1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16577 AN: 152100 Hom.: 1836 Cov.: 31

Gnomad AFR AF: 0.0282

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.0836

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0933

GnomAD3 exomes AF: 0.164 AC: 25547 AN: 155500 Hom.: 3678 AF XY: 0.159 AC XY: 13591 AN XY: 85278

Gnomad AFR exome AF: 0.0244

Gnomad AMR exome AF: 0.217

Gnomad ASJ exome AF: 0.151

Gnomad EAS exome AF: 0.647

Gnomad SAS exome AF: 0.173

Gnomad FIN exome AF: 0.0876

Gnomad NFE exome AF: 0.111

Gnomad OTH exome AF: 0.147

GnomAD4 exome AF: 0.129 AC: 174364 AN: 1355076 Hom.: 17543 Cov.: 31 AF XY: 0.129 AC XY: 86163 AN XY: 665602

Gnomad4 AFR exome AF: 0.0210

Gnomad4 AMR exome AF: 0.201

Gnomad4 ASJ exome AF: 0.145

Gnomad4 EAS exome AF: 0.673

Gnomad4 SAS exome AF: 0.170

Gnomad4 FIN exome AF: 0.0928

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.141

GnomAD4 genome AF: 0.109 AC: 16568 AN: 152218 Hom.: 1830 Cov.: 31 AF XY: 0.113 AC XY: 8382 AN XY: 74424

Gnomad4 AFR AF: 0.0281

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.640

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.0836

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.0919

Alfa AF: 0.111 Hom.: 364

Bravo AF: 0.111

Asia WGS AF: 0.326 AC: 1133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.79
DANN	Benign	0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs3746130; hg19: chr19-5240392; COSMIC: COSV53618893;