19-5231124-T-C

Variant names:

• chr19-5231124-T-C
• rs4807015
• NM_002850.4:c.2155+186A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002850.4(PTPRS):​c.2155+186A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 152,066 control chromosomes in the GnomAD database, including 12,821 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 0.37 (12821 hom., cov: 31)
• Consequence: PTPRS NM_002850.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590
• Publications: 11 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRS	NM_002850.4	c.2155+186A>G		intron_variant	Intron 14 of 37	ENST00000262963.11	NP_002841.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRS	ENST00000262963.11	c.2155+186A>G		intron_variant	Intron 14 of 37	5	NM_002850.4	ENSP00000262963.8

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56853 AN: 151948 Hom.: 12817 Cov.: 31

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.374 AC: 56856 AN: 152066 Hom.: 12821 Cov.: 31 AF XY: 0.375 AC XY: 27893 AN XY: 74314

African (AFR) AF: 0.114 AC: 4741 AN: 41514

American (AMR) AF: 0.360 AC: 5506 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 1429 AN: 3468

East Asian (EAS) AF: 0.707 AC: 3635 AN: 5138

South Asian (SAS) AF: 0.509 AC: 2444 AN: 4806

European-Finnish (FIN) AF: 0.433 AC: 4569 AN: 10560

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.488 AC: 33176 AN: 67968

Other (OTH) AF: 0.379 AC: 801 AN: 2114

Alfa AF: 0.423 Hom.: 22907

Bravo AF: 0.358

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
DANN	Benign	0.12
PhyloP100		-0.059
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)		0.0		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: rs4807015; hg19: chr19-5231135;