19-5269447-T-C

Variant names:

• chr19-5269447-T-C
• rs8110570
• NM_002850.4:c.379+3995A>G

Variant summary

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

The NM_002850.4(PTPRS):​c.379+3995A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 151,422 control chromosomes in the GnomAD database, including 3,362 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 0.18 (3362 hom., cov: 30)
• Consequence: PTPRS NM_002850.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.144
• Publications: 1 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]

ENSG00000296960 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRS	NM_002850.4	c.379+3995A>G		intron_variant	Intron 4 of 37	ENST00000262963.11	NP_002841.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRS	ENST00000262963.11	c.379+3995A>G		intron_variant	Intron 4 of 37	5	NM_002850.4	ENSP00000262963.8

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26815 AN: 151304 Hom.: 3352 Cov.: 30

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.00137

Gnomad SAS AF: 0.0696

Gnomad FIN AF: 0.0881

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.177 AC: 26842 AN: 151422 Hom.: 3362 Cov.: 30 AF XY: 0.172 AC XY: 12698 AN XY: 73942

African (AFR) AF: 0.353 AC: 14581 AN: 41252

American (AMR) AF: 0.119 AC: 1813 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 490 AN: 3466

East Asian (EAS) AF: 0.00137 AC: 7 AN: 5110

South Asian (SAS) AF: 0.0695 AC: 332 AN: 4780

European-Finnish (FIN) AF: 0.0881 AC: 923 AN: 10480

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8111 AN: 67826

Other (OTH) AF: 0.178 AC: 372 AN: 2094

Alfa AF: 0.142 Hom.: 246

Bravo AF: 0.188

Asia WGS AF: 0.0480 AC: 168 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	4.4
DANN	Benign	0.51
PhyloP100		-0.14
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: rs8110570; hg19: chr19-5269458;