rs758512

Variant names:

• chr19-5290873-C-G
• rs758512
• NM_002850.4:c.-94-4639G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-5290873-C-G
• chr19-5290873-C-T

Variant summary

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

The NM_002850.4(PTPRS):​c.-94-4639G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 151,766 control chromosomes in the GnomAD database, including 2,039 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 0.15 (2039 hom., cov: 31)
• Consequence: PTPRS NM_002850.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0480
• 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002850.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRS	NM_002850.4	MANE Select	c.-94-4639G>C		intron	N/A	NP_002841.3
	PTPRS	NM_001394011.1		c.-94-4639G>C		intron	N/A	NP_001380940.1
	PTPRS	NM_001394012.1		c.-94-4639G>C		intron	N/A	NP_001380941.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRS	ENST00000262963.11	TSL:5 MANE Select	c.-94-4639G>C		intron	N/A	ENSP00000262963.8	Q13332-1
	PTPRS	ENST00000588552.5	TSL:1	n.141-4639G>C		intron	N/A
	PTPRS	ENST00000919618.1		c.-94-4639G>C		intron	N/A	ENSP00000589677.1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23269 AN: 151648 Hom.: 2032 Cov.: 31

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.00138

Gnomad SAS AF: 0.0909

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.153 AC: 23283 AN: 151766 Hom.: 2039 Cov.: 31 AF XY: 0.147 AC XY: 10911 AN XY: 74160

African (AFR) AF: 0.207 AC: 8567 AN: 41348

American (AMR) AF: 0.122 AC: 1862 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 590 AN: 3466

East Asian (EAS) AF: 0.00138 AC: 7 AN: 5058

South Asian (SAS) AF: 0.0916 AC: 441 AN: 4814

European-Finnish (FIN) AF: 0.105 AC: 1111 AN: 10566

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10158 AN: 67924

Other (OTH) AF: 0.166 AC: 350 AN: 2114

Alfa AF: 0.0465 Hom.: 48

Bravo AF: 0.157

Asia WGS AF: 0.0500 AC: 175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.3
DANN	Benign	0.84
PhyloP100		-0.048
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: rs758512; hg19: chr19-5290884;