19-5206764-A-G

Variant names:

• chr19-5206764-A-G
• rs1143700
• NM_002850.4:c.*10T>C

Variant summary

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

The NM_002850.4(PTPRS):​c.*10T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.815 in 1,611,932 control chromosomes in the GnomAD database, including 537,587 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 (55848 hom., cov: 33)
  • Exomes 𝑓: 0.81 (481739 hom.)
• Consequence: PTPRS NM_002850.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.331
• Publications: 17 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=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRS	NM_002850.4	c.*10T>C		3_prime_UTR_variant	Exon 38 of 38	ENST00000262963.11	NP_002841.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRS	ENST00000262963.11	c.*10T>C		3_prime_UTR_variant	Exon 38 of 38	5	NM_002850.4	ENSP00000262963.8

Frequencies

GnomAD3 genomes AF: 0.852 AC: 129643 AN: 152080 Hom.: 55799 Cov.: 33

Gnomad AFR AF: 0.963

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.803

Gnomad ASJ AF: 0.827

Gnomad EAS AF: 0.662

Gnomad SAS AF: 0.789

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.821

Gnomad OTH AF: 0.842

GnomAD2 exomes AF: 0.808 AC: 201079 AN: 249002 AF XY: 0.805

Gnomad AFR exome AF: 0.965

Gnomad AMR exome AF: 0.780

Gnomad ASJ exome AF: 0.813

Gnomad EAS exome AF: 0.678

Gnomad FIN exome AF: 0.816

Gnomad NFE exome AF: 0.821

Gnomad OTH exome AF: 0.813

GnomAD4 exome AF: 0.811 AC: 1183773 AN: 1459734 Hom.: 481739 Cov.: 40 AF XY: 0.809 AC XY: 587922 AN XY: 726320

African (AFR) AF: 0.965 AC: 32257 AN: 33432

American (AMR) AF: 0.787 AC: 35184 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.814 AC: 21233 AN: 26090

East Asian (EAS) AF: 0.652 AC: 25850 AN: 39622

South Asian (SAS) AF: 0.777 AC: 66918 AN: 86176

European-Finnish (FIN) AF: 0.816 AC: 43543 AN: 53376

Middle Eastern (MID) AF: 0.792 AC: 4558 AN: 5752

European-Non Finnish (NFE) AF: 0.816 AC: 906035 AN: 1110292

Other (OTH) AF: 0.799 AC: 48195 AN: 60294

GnomAD4 genome AF: 0.852 AC: 129744 AN: 152198 Hom.: 55848 Cov.: 33 AF XY: 0.850 AC XY: 63250 AN XY: 74398

African (AFR) AF: 0.963 AC: 39991 AN: 41546

American (AMR) AF: 0.802 AC: 12260 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.827 AC: 2867 AN: 3468

East Asian (EAS) AF: 0.663 AC: 3420 AN: 5162

South Asian (SAS) AF: 0.788 AC: 3794 AN: 4814

European-Finnish (FIN) AF: 0.834 AC: 8842 AN: 10602

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.821 AC: 55795 AN: 67996

Other (OTH) AF: 0.841 AC: 1777 AN: 2114

Alfa AF: 0.828 Hom.: 56125

Bravo AF: 0.856

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	11
DANN	Benign	0.86
PhyloP100		0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1143700; hg19: chr19-5206775; COSMIC: COSV53643378; COSMIC: COSV53643378;