rs740058

Positions:

• chr19-5288171-A-C
• chr19-5288171-A-G

Variant summary

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

The NM_002850.4(PTPRS):​c.-94-1937T>G 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 152,140 control chromosomes in the GnomAD database, including 2,886 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 (2886 hom., cov: 32)
• Consequence: PTPRS NM_002850.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.841

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRS	NM_002850.4	c.-94-1937T>G		intron_variant		ENST00000262963.11	NP_002841.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRS	ENST00000262963.11	c.-94-1937T>G		intron_variant		5	NM_002850.4	ENSP00000262963.8
PTPRS	ENST00000588552.5	n.141-1937T>G		intron_variant		1
PTPRS	ENST00000586065.1	n.58-1937T>G		intron_variant		5
PTPRS	ENST00000591760.5	n.113-1937T>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28090 AN: 152022 Hom.: 2888 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.00597

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.185 AC: 28087 AN: 152140 Hom.: 2886 Cov.: 32 AF XY: 0.181 AC XY: 13431 AN XY: 74390

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.00579

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.170

Alfa AF: 0.214 Hom.: 7496

Bravo AF: 0.180

Asia WGS AF: 0.0770 AC: 269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.43
DANN	Benign	0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs740058; hg19: chr19-5288182;