rs2230611

Variant names:

• chr19-5212471-G-A
• rs2230611
• NM_002850.4:c.4635C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-5212471-G-A
• chr19-5212471-G-C

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.4635C>T​(p.Arg1545Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,593,162 control chromosomes in the GnomAD database, including 12,169 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 (1278 hom., cov: 33)
  • Exomes 𝑓: 0.12 (10891 hom.)
• Consequence: PTPRS NM_002850.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.78
• 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=-0.56).
• BP7: Synonymous conserved (PhyloP=-4.78 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRS	NM_002850.4	c.4635C>T	p.Arg1545Arg	synonymous_variant	Exon 31 of 38	ENST00000262963.11	NP_002841.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRS	ENST00000262963.11	c.4635C>T	p.Arg1545Arg	synonymous_variant	Exon 31 of 38	5	NM_002850.4	ENSP00000262963.8

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18685 AN: 152088 Hom.: 1277 Cov.: 33

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.0688

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.138

GnomAD2 exomes AF: 0.136 AC: 29287 AN: 214790 AF XY: 0.132

Gnomad AFR exome AF: 0.107

Gnomad AMR exome AF: 0.279

Gnomad ASJ exome AF: 0.0968

Gnomad EAS exome AF: 0.0615

Gnomad FIN exome AF: 0.132

Gnomad NFE exome AF: 0.104

Gnomad OTH exome AF: 0.132

GnomAD4 exome AF: 0.118 AC: 169764 AN: 1440956 Hom.: 10891 Cov.: 35 AF XY: 0.118 AC XY: 84706 AN XY: 714950

African (AFR) AF: 0.108 AC: 3550 AN: 32966

American (AMR) AF: 0.276 AC: 11456 AN: 41574

Ashkenazi Jewish (ASJ) AF: 0.0990 AC: 2551 AN: 25770

East Asian (EAS) AF: 0.0685 AC: 2646 AN: 38628

South Asian (SAS) AF: 0.165 AC: 13751 AN: 83542

European-Finnish (FIN) AF: 0.139 AC: 7170 AN: 51408

Middle Eastern (MID) AF: 0.113 AC: 652 AN: 5746

European-Non Finnish (NFE) AF: 0.110 AC: 120883 AN: 1101776

Other (OTH) AF: 0.119 AC: 7105 AN: 59546

GnomAD4 genome AF: 0.123 AC: 18692 AN: 152206 Hom.: 1278 Cov.: 33 AF XY: 0.125 AC XY: 9332 AN XY: 74408

African (AFR) AF: 0.106 AC: 4412 AN: 41542

American (AMR) AF: 0.225 AC: 3432 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 364 AN: 3472

East Asian (EAS) AF: 0.0688 AC: 356 AN: 5178

South Asian (SAS) AF: 0.180 AC: 869 AN: 4816

European-Finnish (FIN) AF: 0.138 AC: 1464 AN: 10594

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7415 AN: 68008

Other (OTH) AF: 0.137 AC: 289 AN: 2112

Alfa AF: 0.115 Hom.: 2103

Bravo AF: 0.128

Asia WGS AF: 0.137 AC: 476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.30
DANN	Benign	0.80
PhyloP100		-4.8
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2230611; hg19: chr19-5212482; COSMIC: COSV53614219; COSMIC: COSV53614219;