rs8105746

Variant names:

• chr19-5200845-C-T
• rs8105746
• ENST00000588552.5:n.4719+7077G>A

Variant summary

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

The ENST00000588552.5(PTPRS):​n.4719+7077G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,002 control chromosomes in the GnomAD database, including 5,752 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 0.21 (5752 hom., cov: 32)
• Consequence: PTPRS ENST00000588552.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.871
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRS	ENST00000588552.5	n.4719+7077G>A		intron_variant	Intron 29 of 30	1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32186 AN: 151884 Hom.: 5727 Cov.: 32

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0957

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0570

Gnomad FIN AF: 0.0905

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.212 AC: 32256 AN: 152002 Hom.: 5752 Cov.: 32 AF XY: 0.206 AC XY: 15307 AN XY: 74316

African (AFR) AF: 0.493 AC: 20386 AN: 41388

American (AMR) AF: 0.110 AC: 1677 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0957 AC: 332 AN: 3468

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5190

South Asian (SAS) AF: 0.0562 AC: 271 AN: 4818

European-Finnish (FIN) AF: 0.0905 AC: 957 AN: 10578

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8070 AN: 67982

Other (OTH) AF: 0.179 AC: 378 AN: 2112

Alfa AF: 0.142 Hom.: 2803

Bravo AF: 0.226

Asia WGS AF: 0.0730 AC: 256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	7.4
DANN	Benign	0.62
PhyloP100		-0.87

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8105746; hg19: chr19-5200856;