rs1143699

Variant names:

• chr19-5210751-G-A
• rs1143699
• NM_002850.4:c.5289C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002850.4(PTPRS):​c.5289C>T​(p.Asp1763Asp) 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
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PTPRS	NM_002850.4	c.5289C>T	p.Asp1763Asp	synonymous_variant	Exon 34 of 38	ENST00000262963.11	NP_002841.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRS	ENST00000262963.11	c.5289C>T	p.Asp1763Asp	synonymous_variant	Exon 34 of 38	5	NM_002850.4	ENSP00000262963.8

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

GnomAD2 exomes AF: 0.0876 AC: 21998 AN: 251126 AF XY: 0.0859

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 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

African (AFR) AF: 0.197 AC: 6608 AN: 33476

American (AMR) AF: 0.0530 AC: 2369 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0895 AC: 2339 AN: 26134

East Asian (EAS) AF: 0.000277 AC: 11 AN: 39698

South Asian (SAS) AF: 0.0494 AC: 4263 AN: 86256

European-Finnish (FIN) AF: 0.0823 AC: 4387 AN: 53312

Middle Eastern (MID) AF: 0.0711 AC: 410 AN: 5768

European-Non Finnish (NFE) AF: 0.105 AC: 116893 AN: 1111998

Other (OTH) AF: 0.0965 AC: 5828 AN: 60394

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

African (AFR) AF: 0.191 AC: 7942 AN: 41536

American (AMR) AF: 0.0822 AC: 1258 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0832 AC: 289 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.0501 AC: 242 AN: 4832

European-Finnish (FIN) AF: 0.0819 AC: 870 AN: 10620

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7253 AN: 68014

Other (OTH) AF: 0.112 AC: 237 AN: 2114

Alfa AF: 0.107 Hom.: 2814

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
PhyloP100		0.53
Mutation Taster		=93/7	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1143699; hg19: chr19-5210762; COSMIC: COSV108077583; COSMIC: COSV108077583;