19-5236155-C-T

Variant names:

• chr19-5236155-C-T
• rs2379609
• NM_002850.4:c.1849+2764G>A

Variant summary

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

The NM_002850.4(PTPRS):​c.1849+2764G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 152,254 control chromosomes in the GnomAD database, including 50,814 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 0.81 (50814 hom., cov: 33)
• Consequence: PTPRS NM_002850.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.947 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.1849+2764G>A		intron	N/A	NP_002841.3
	PTPRS	NM_001394011.1		c.1810+2764G>A		intron	N/A	NP_001380940.1
	PTPRS	NM_001394012.1		c.1810+2764G>A		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.1849+2764G>A		intron	N/A	ENSP00000262963.8	Q13332-1
	PTPRS	ENST00000587303.5	TSL:1	c.1849+2764G>A		intron	N/A	ENSP00000467537.1	Q13332-1
	PTPRS	ENST00000588012.5	TSL:1	c.1810+2764G>A		intron	N/A	ENSP00000465443.1	Q13332-6

Frequencies

GnomAD3 genomes AF: 0.812 AC: 123475 AN: 152136 Hom.: 50772 Cov.: 33

Gnomad AFR AF: 0.955

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.804

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

GnomAD4 genome AF: 0.812 AC: 123571 AN: 152254 Hom.: 50814 Cov.: 33 AF XY: 0.805 AC XY: 59946 AN XY: 74424

African (AFR) AF: 0.955 AC: 39684 AN: 41570

American (AMR) AF: 0.768 AC: 11751 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 2412 AN: 3472

East Asian (EAS) AF: 0.773 AC: 4003 AN: 5176

South Asian (SAS) AF: 0.756 AC: 3645 AN: 4822

European-Finnish (FIN) AF: 0.711 AC: 7520 AN: 10584

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.766 AC: 52092 AN: 68014

Other (OTH) AF: 0.802 AC: 1696 AN: 2114

Alfa AF: 0.776 Hom.: 88626

Bravo AF: 0.820

Asia WGS AF: 0.758 AC: 2634 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.061
DANN	Benign	0.59
PhyloP100		-1.8
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: rs2379609; hg19: chr19-5236166;