chr19-5267740-C-T

Position:

• chr19-5267740-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.380-2544G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 139,902 control chromosomes in the GnomAD database, including 3,274 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 0.18 (3274 hom., cov: 22)
• Consequence: PTPRS NM_002850.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.15

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]

PTPRS (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRS	NM_002850.4	c.380-2544G>A		intron_variant		ENST00000262963.11	NP_002841.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRS	ENST00000262963.11	c.380-2544G>A		intron_variant		5	NM_002850.4	ENSP00000262963.8

Frequencies

GnomAD3 genomes AF: 0.184 AC: 25768 AN: 139810 Hom.: 3234 Cov.: 22

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.0611

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.0432

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.185 AC: 25864 AN: 139902 Hom.: 3274 Cov.: 22 AF XY: 0.183 AC XY: 12317 AN XY: 67208

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.0431

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.181

Alfa AF: 0.108 Hom.: 588

Bravo AF: 0.206

Asia WGS AF: 0.141 AC: 491 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.12
DANN	Benign	0.59

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: rs1034863; hg19: chr19-5267751;