rs4807016

Positions:

• chr19-5258479-G-A
• chr19-5258479-G-C
• chr19-5258479-G-T

Variant summary

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

The NM_002850.4(PTPRS):​c.596-352C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 151,738 control chromosomes in the GnomAD database, including 8,616 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 0.32 (8616 hom., cov: 32)
• Consequence: PTPRS NM_002850.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRS	NM_002850.4	c.596-352C>T		intron_variant		ENST00000262963.11	NP_002841.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRS	ENST00000262963.11	c.596-352C>T		intron_variant		5	NM_002850.4	ENSP00000262963.8

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48492 AN: 151620 Hom.: 8607 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.322

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.320 AC: 48539 AN: 151738 Hom.: 8616 Cov.: 32 AF XY: 0.321 AC XY: 23821 AN XY: 74142

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.729

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.337

Gnomad4 OTH AF: 0.325

Alfa AF: 0.338 Hom.: 11725

Bravo AF: 0.323

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.52

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: rs4807016; hg19: chr19-5258490;