chr19-5216272-G-C

Variant names:

• chr19-5216272-G-C
• rs10413063
• NM_002850.4:c.4096+448C>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.4096+448C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 151,966 control chromosomes in the GnomAD database, including 22,020 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 0.51 (22020 hom., cov: 32)
• Consequence: PTPRS NM_002850.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.143
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002850.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRS	NM_002850.4	MANE Select	c.4096+448C>G		intron	N/A	NP_002841.3
	PTPRS	NM_001394011.1		c.4030+448C>G		intron	N/A	NP_001380940.1
	PTPRS	NM_001394012.1		c.4010-677C>G		intron	N/A	NP_001380941.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRS	ENST00000262963.11	TSL:5 MANE Select	c.4096+448C>G		intron	N/A	ENSP00000262963.8
	PTPRS	ENST00000587303.5	TSL:1	c.4096+448C>G		intron	N/A	ENSP00000467537.1
	PTPRS	ENST00000588012.5	TSL:1	c.3983-677C>G		intron	N/A	ENSP00000465443.1

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76822 AN: 151848 Hom.: 21991 Cov.: 32

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.506 AC: 76902 AN: 151966 Hom.: 22020 Cov.: 32 AF XY: 0.504 AC XY: 37419 AN XY: 74266

African (AFR) AF: 0.785 AC: 32530 AN: 41444

American (AMR) AF: 0.466 AC: 7122 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1513 AN: 3470

East Asian (EAS) AF: 0.118 AC: 610 AN: 5182

South Asian (SAS) AF: 0.349 AC: 1679 AN: 4806

European-Finnish (FIN) AF: 0.474 AC: 4998 AN: 10544

Middle Eastern (MID) AF: 0.438 AC: 127 AN: 290

European-Non Finnish (NFE) AF: 0.397 AC: 26958 AN: 67928

Other (OTH) AF: 0.491 AC: 1039 AN: 2114

Alfa AF: 0.472 Hom.: 2288

Bravo AF: 0.518

Asia WGS AF: 0.292 AC: 1015 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.3
DANN	Benign	0.42
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: rs10413063; hg19: chr19-5216283;