chr19-5274373-C-T

Position:

• chr19-5274373-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.92-29G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,592,672 control chromosomes in the GnomAD database, including 16,234 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 0.15 (1818 hom., cov: 32)
  • Exomes 𝑓: 0.14 (14416 hom.)
• Consequence: PTPRS NM_002850.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRS	NM_002850.4	c.92-29G>A		intron_variant		ENST00000262963.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRS	ENST00000262963.11	c.92-29G>A		intron_variant		5	NM_002850.4	A1

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22368 AN: 151554 Hom.: 1811 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.0883

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.122

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.150

GnomAD3 exomes AF: 0.156 AC: 37601 AN: 240264 Hom.: 3497 AF XY: 0.151 AC XY: 19763 AN XY: 131000

Gnomad AFR exome AF: 0.160

Gnomad AMR exome AF: 0.307

Gnomad ASJ exome AF: 0.0919

Gnomad EAS exome AF: 0.105

Gnomad SAS exome AF: 0.150

Gnomad FIN exome AF: 0.109

Gnomad NFE exome AF: 0.135

Gnomad OTH exome AF: 0.151

GnomAD4 exome AF: 0.136 AC: 195752 AN: 1441000 Hom.: 14416 Cov.: 32 AF XY: 0.136 AC XY: 96681 AN XY: 713392

Gnomad4 AFR exome AF: 0.161

Gnomad4 AMR exome AF: 0.297

Gnomad4 ASJ exome AF: 0.0891

Gnomad4 EAS exome AF: 0.0997

Gnomad4 SAS exome AF: 0.149

Gnomad4 FIN exome AF: 0.107

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.133

GnomAD4 genome AF: 0.148 AC: 22397 AN: 151672 Hom.: 1818 Cov.: 32 AF XY: 0.148 AC XY: 10999 AN XY: 74114

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.0883

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.153

Alfa AF: 0.123 Hom.: 1534

Bravo AF: 0.157

Asia WGS AF: 0.145 AC: 506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.27
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs1034917; hg19: chr19-5274384;