chr19-5254959-T-C

Variant names:

• chr19-5254959-T-C
• rs17130
• NM_002850.4:c.718+1149A>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.718+1149A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 152,090 control chromosomes in the GnomAD database, including 8,459 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 0.32 (8459 hom., cov: 32)
• Consequence: PTPRS NM_002850.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.744
• Publications: 10 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.689 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.718+1149A>G		intron	N/A	NP_002841.3
	PTPRS	NM_001394011.1		c.679+3058A>G		intron	N/A	NP_001380940.1
	PTPRS	NM_001394012.1		c.679+3058A>G		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.718+1149A>G		intron	N/A	ENSP00000262963.8	Q13332-1
	PTPRS	ENST00000587303.5	TSL:1	c.718+1149A>G		intron	N/A	ENSP00000467537.1	Q13332-1
	PTPRS	ENST00000588012.5	TSL:1	c.679+3058A>G		intron	N/A	ENSP00000465443.1	Q13332-6

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48948 AN: 151972 Hom.: 8451 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.322 AC: 48978 AN: 152090 Hom.: 8459 Cov.: 32 AF XY: 0.323 AC XY: 24023 AN XY: 74320

African (AFR) AF: 0.248 AC: 10307 AN: 41482

American (AMR) AF: 0.334 AC: 5103 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1122 AN: 3470

East Asian (EAS) AF: 0.708 AC: 3659 AN: 5166

South Asian (SAS) AF: 0.341 AC: 1647 AN: 4826

European-Finnish (FIN) AF: 0.303 AC: 3194 AN: 10556

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22916 AN: 67978

Other (OTH) AF: 0.316 AC: 667 AN: 2110

Alfa AF: 0.333 Hom.: 16175

Bravo AF: 0.322

Asia WGS AF: 0.445 AC: 1547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.54
PhyloP100		-0.74
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: rs17130; hg19: chr19-5254970;