chr19-5258479-G-A

Variant names:

• chr19-5258479-G-A
• rs4807016
• NM_002850.4:c.596-352C>T

Variant summary

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

The ENST00000262963.11(PTPRS):​c.596-352C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 151,738 control chromosomes in the GnomAD database, including 8,616 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 (8616 hom., cov: 32)
• Consequence: PTPRS ENST00000262963.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000262963.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRS	NM_002850.4	MANE Select	c.596-352C>T		intron	N/A	NP_002841.3
	PTPRS	NM_001394011.1		c.569-352C>T		intron	N/A	NP_001380940.1
	PTPRS	NM_001394012.1		c.569-352C>T		intron	N/A	NP_001380941.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRS	ENST00000262963.11	TSL:5 MANE Select	c.596-352C>T		intron	N/A	ENSP00000262963.8
	PTPRS	ENST00000587303.5	TSL:1	c.596-352C>T		intron	N/A	ENSP00000467537.1
	PTPRS	ENST00000588012.5	TSL:1	c.569-352C>T		intron	N/A	ENSP00000465443.1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48492 AN: 151620 Hom.: 8607 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.320 AC: 48539 AN: 151738 Hom.: 8616 Cov.: 32 AF XY: 0.321 AC XY: 23821 AN XY: 74142

African (AFR) AF: 0.212 AC: 8731 AN: 41144

American (AMR) AF: 0.398 AC: 6064 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1314 AN: 3470

East Asian (EAS) AF: 0.729 AC: 3776 AN: 5182

South Asian (SAS) AF: 0.420 AC: 2019 AN: 4810

European-Finnish (FIN) AF: 0.254 AC: 2686 AN: 10582

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

European-Non Finnish (NFE) AF: 0.337 AC: 22908 AN: 67994

Other (OTH) AF: 0.325 AC: 684 AN: 2104

Alfa AF: 0.338 Hom.: 16589

Bravo AF: 0.323

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.52
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4807016; hg19: chr19-5258490;