19-5246706-C-T

Variant names:

• chr19-5246706-C-T
• rs10415488
• NM_002850.4:c.719-661G>A

Variant summary

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

The NM_002850.4(PTPRS):​c.719-661G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 151,986 control chromosomes in the GnomAD database, including 30,517 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 0.63 (30517 hom., cov: 31)
• Consequence: PTPRS NM_002850.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.923

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRS	NM_002850.4	c.719-661G>A		intron_variant	Intron 9 of 37	ENST00000262963.11	NP_002841.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRS	ENST00000262963.11	c.719-661G>A		intron_variant	Intron 9 of 37	5	NM_002850.4	ENSP00000262963.8

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95722 AN: 151868 Hom.: 30471 Cov.: 31

Gnomad AFR AF: 0.706

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.630 AC: 95817 AN: 151986 Hom.: 30517 Cov.: 31 AF XY: 0.628 AC XY: 46668 AN XY: 74274

Gnomad4 AFR AF: 0.706

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.584

Gnomad4 EAS AF: 0.722

Gnomad4 SAS AF: 0.548

Gnomad4 FIN AF: 0.630

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.603

Alfa AF: 0.603 Hom.: 35148

Bravo AF: 0.628

Asia WGS AF: 0.592 AC: 2058 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.48
DANN	Benign	0.52

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: rs10415488; hg19: chr19-5246717;