19-5211613-G-A

Position:

• chr19-5211613-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_002850.4(PTPRS):​c.5211C>T​(p.Asn1737=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00403 in 1,610,196 control chromosomes in the GnomAD database, including 132 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0066 (20 hom., cov: 33)
  • Exomes 𝑓: 0.0038 (112 hom.)
• Consequence: PTPRS NM_002850.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.767

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 19-5211613-G-A is Benign according to our data. Variant chr19-5211613-G-A is described in ClinVar as [Benign]. Clinvar id is 769948.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.767 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00376 (5480/1457918) while in subpopulation AMR AF= 0.0355 (1583/44644). AF 95% confidence interval is 0.034. There are 112 homozygotes in gnomad4_exome. There are 2532 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1005 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRS	NM_002850.4	c.5211C>T	p.Asn1737=	synonymous_variant	33/38	ENST00000262963.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRS	ENST00000262963.11	c.5211C>T	p.Asn1737=	synonymous_variant	33/38	5	NM_002850.4	A1

Frequencies

GnomAD3 genomes AF: 0.00660 AC: 1005 AN: 152160 Hom.: 20 Cov.: 33

Gnomad AFR AF: 0.000603

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0163

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00712

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0505

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00203

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.0113 AC: 2834 AN: 251032 Hom.: 64 AF XY: 0.00966 AC XY: 1311 AN XY: 135692

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.0387

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00571

Gnomad SAS exome AF: 0.000327

Gnomad FIN exome AF: 0.0506

Gnomad NFE exome AF: 0.00203

Gnomad OTH exome AF: 0.00801

GnomAD4 exome AF: 0.00376 AC: 5480 AN: 1457918 Hom.: 112 Cov.: 33 AF XY: 0.00350 AC XY: 2532 AN XY: 724364

Gnomad4 AFR exome AF: 0.000629

Gnomad4 AMR exome AF: 0.0355

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00604

Gnomad4 SAS exome AF: 0.000371

Gnomad4 FIN exome AF: 0.0497

Gnomad4 NFE exome AF: 0.000647

Gnomad4 OTH exome AF: 0.00394

GnomAD4 genome AF: 0.00660 AC: 1005 AN: 152278 Hom.: 20 Cov.: 33 AF XY: 0.00897 AC XY: 668 AN XY: 74456

Gnomad4 AFR AF: 0.000602

Gnomad4 AMR AF: 0.0163

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00714

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.0505

Gnomad4 NFE AF: 0.00203

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00273 Hom.: 1

Bravo AF: 0.00488

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

PTPRS-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	9.2
DANN	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs115796999; hg19: chr19-5211624;