19-5200845-C-T

Position:

• chr19-5200845-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000588552.5(PTPRS):​n.4719+7077G>A variant causes a intron, non coding transcript 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, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.871

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRS	ENST00000588552.5	n.4719+7077G>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.493

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.0957

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0562

Gnomad4 FIN AF: 0.0905

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.179

Alfa AF: 0.127 Hom.: 1528

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8105746; hg19: chr19-5200856;