19-5220889-T-C

Position:

• chr19-5220889-T-C

Variant summary

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

The NM_002850.4(PTPRS):​c.3455+111A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 1,293,374 control chromosomes in the GnomAD database, including 423,164 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 0.85 (54807 hom., cov: 32)
  • Exomes 𝑓: 0.80 (368357 hom.)
• Consequence: PTPRS NM_002850.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRS	NM_002850.4	c.3455+111A>G		intron_variant		ENST00000262963.11	NP_002841.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRS	ENST00000262963.11	c.3455+111A>G		intron_variant		5	NM_002850.4	ENSP00000262963	A1

Frequencies

GnomAD3 genomes AF: 0.845 AC: 128460 AN: 152018 Hom.: 54759 Cov.: 32

Gnomad AFR AF: 0.959

Gnomad AMI AF: 0.825

Gnomad AMR AF: 0.791

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.809

Gnomad OTH AF: 0.838

GnomAD4 exome AF: 0.802 AC: 915417 AN: 1141238 Hom.: 368357 AF XY: 0.801 AC XY: 454941 AN XY: 568064

Gnomad4 AFR exome AF: 0.962

Gnomad4 AMR exome AF: 0.780

Gnomad4 ASJ exome AF: 0.776

Gnomad4 EAS exome AF: 0.701

Gnomad4 SAS exome AF: 0.779

Gnomad4 FIN exome AF: 0.803

Gnomad4 NFE exome AF: 0.805

Gnomad4 OTH exome AF: 0.792

GnomAD4 genome AF: 0.845 AC: 128561 AN: 152136 Hom.: 54807 Cov.: 32 AF XY: 0.843 AC XY: 62685 AN XY: 74376

Gnomad4 AFR AF: 0.959

Gnomad4 AMR AF: 0.790

Gnomad4 ASJ AF: 0.790

Gnomad4 EAS AF: 0.722

Gnomad4 SAS AF: 0.782

Gnomad4 FIN AF: 0.823

Gnomad4 NFE AF: 0.809

Gnomad4 OTH AF: 0.836

Alfa AF: 0.808 Hom.: 19461

Bravo AF: 0.850

Asia WGS AF: 0.728 AC: 2536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.029
DANN	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs10412973; hg19: chr19-5220900;