rs7254570

Variant names:

• chr19-5278867-C-A
• rs7254570
• NM_002850.4:c.92-4523G>T

Variant summary

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

The NM_002850.4(PTPRS):​c.92-4523G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.93 in 152,072 control chromosomes in the GnomAD database, including 65,949 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 0.93 (65949 hom., cov: 29)
• Consequence: PTPRS NM_002850.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRS	NM_002850.4	c.92-4523G>T		intron_variant	Intron 2 of 37	ENST00000262963.11	NP_002841.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRS	ENST00000262963.11	c.92-4523G>T		intron_variant	Intron 2 of 37	5	NM_002850.4	ENSP00000262963.8

Frequencies

GnomAD3 genomes AF: 0.930 AC: 141276 AN: 151954 Hom.: 65887 Cov.: 29

Gnomad AFR AF: 0.981

Gnomad AMI AF: 0.891

Gnomad AMR AF: 0.930

Gnomad ASJ AF: 0.956

Gnomad EAS AF: 0.802

Gnomad SAS AF: 0.802

Gnomad FIN AF: 0.839

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.930

Gnomad OTH AF: 0.937

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

GnomAD4 genome AF: 0.930 AC: 141398 AN: 152072 Hom.: 65949 Cov.: 29 AF XY: 0.922 AC XY: 68496 AN XY: 74328

African (AFR) AF: 0.981 AC: 40704 AN: 41494

American (AMR) AF: 0.931 AC: 14208 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.956 AC: 3319 AN: 3470

East Asian (EAS) AF: 0.801 AC: 4133 AN: 5158

South Asian (SAS) AF: 0.802 AC: 3849 AN: 4800

European-Finnish (FIN) AF: 0.839 AC: 8864 AN: 10564

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.930 AC: 63248 AN: 68006

Other (OTH) AF: 0.938 AC: 1978 AN: 2108

Alfa AF: 0.929 Hom.: 24295

Bravo AF: 0.940

Asia WGS AF: 0.817 AC: 2843 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.57
DANN	Benign	0.24
PhyloP100		-1.3
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: rs7254570; hg19: chr19-5278878;