19-5240381-C-T

Variant names:

• chr19-5240381-C-T
• rs3746130
• NM_002850.4:c.1571-49G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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 -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 rank	MANE	Protein	UniProt
PTPRS	NM_002850.4	c.1571-49G>A		intron_variant	Intron 11 of 37	ENST00000262963.11	NP_002841.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRS	ENST00000262963.11	c.1571-49G>A		intron_variant	Intron 11 of 37	5	NM_002850.4	ENSP00000262963.8

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

GnomAD2 exomes AF: 0.164 AC: 25547 AN: 155500 AF XY: 0.159

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 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

African (AFR) AF: 0.0210 AC: 628 AN: 29932

American (AMR) AF: 0.201 AC: 6111 AN: 30442

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 3158 AN: 21722

East Asian (EAS) AF: 0.673 AC: 23286 AN: 34592

South Asian (SAS) AF: 0.170 AC: 12076 AN: 71072

European-Finnish (FIN) AF: 0.0928 AC: 4456 AN: 48024

Middle Eastern (MID) AF: 0.127 AC: 611 AN: 4808

European-Non Finnish (NFE) AF: 0.110 AC: 116188 AN: 1058902

Other (OTH) AF: 0.141 AC: 7850 AN: 55582

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

African (AFR) AF: 0.0281 AC: 1168 AN: 41562

American (AMR) AF: 0.137 AC: 2103 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 532 AN: 3470

East Asian (EAS) AF: 0.640 AC: 3295 AN: 5150

South Asian (SAS) AF: 0.180 AC: 866 AN: 4820

European-Finnish (FIN) AF: 0.0836 AC: 888 AN: 10616

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7417 AN: 67984

Other (OTH) AF: 0.0919 AC: 194 AN: 2112

Alfa AF: 0.112 Hom.: 780

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
PhyloP100		-0.051
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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