19-5267740-C-T

Variant names:

• chr19-5267740-C-T
• rs1034863
• NM_002850.4:c.380-2544G>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.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
• Publications: 2 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]

ENSG00000296960 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PTPRS	NM_002850.4	c.380-2544G>A		intron_variant	Intron 4 of 37	ENST00000262963.11	NP_002841.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRS	ENST00000262963.11	c.380-2544G>A		intron_variant	Intron 4 of 37	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

African (AFR) AF: 0.358 AC: 13031 AN: 36416

American (AMR) AF: 0.213 AC: 2889 AN: 13582

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 599 AN: 3394

East Asian (EAS) AF: 0.0431 AC: 204 AN: 4728

South Asian (SAS) AF: 0.151 AC: 655 AN: 4334

European-Finnish (FIN) AF: 0.107 AC: 903 AN: 8442

Middle Eastern (MID) AF: 0.183 AC: 51 AN: 278

European-Non Finnish (NFE) AF: 0.108 AC: 7125 AN: 65896

Other (OTH) AF: 0.181 AC: 353 AN: 1948

Alfa AF: 0.145 Hom.: 2549

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
PhyloP100		-3.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1034863; hg19: chr19-5267751;