chr19-5269020-G-C

Variant names:

• chr19-5269020-G-C
• rs933394
• NM_002850.4:c.380-3824C>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.380-3824C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0438 in 152,280 control chromosomes in the GnomAD database, including 180 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 0.044 (180 hom., cov: 31)
• Consequence: PTPRS NM_002850.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.808
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0536 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.380-3824C>G		intron	N/A	NP_002841.3
	PTPRS	NM_001394011.1		c.380-3824C>G		intron	N/A	NP_001380940.1
	PTPRS	NM_001394012.1		c.380-3824C>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.380-3824C>G		intron	N/A	ENSP00000262963.8
	PTPRS	ENST00000587303.5	TSL:1	c.380-3824C>G		intron	N/A	ENSP00000467537.1
	PTPRS	ENST00000588012.5	TSL:1	c.380-3824C>G		intron	N/A	ENSP00000465443.1

Frequencies

GnomAD3 genomes AF: 0.0438 AC: 6662 AN: 152162 Hom.: 179 Cov.: 31

Gnomad AFR AF: 0.0334

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0403

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0277

Gnomad FIN AF: 0.0239

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0551

Gnomad OTH AF: 0.0497

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

GnomAD4 genome AF: 0.0438 AC: 6670 AN: 152280 Hom.: 180 Cov.: 31 AF XY: 0.0418 AC XY: 3110 AN XY: 74458

African (AFR) AF: 0.0335 AC: 1394 AN: 41566

American (AMR) AF: 0.0403 AC: 617 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 382 AN: 3470

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5166

South Asian (SAS) AF: 0.0274 AC: 132 AN: 4826

European-Finnish (FIN) AF: 0.0239 AC: 254 AN: 10624

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0551 AC: 3747 AN: 68006

Other (OTH) AF: 0.0492 AC: 104 AN: 2114

Alfa AF: 0.0504 Hom.: 22

Bravo AF: 0.0441

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.37
PhyloP100		0.81
Mutation Taster		=100/0	polymorphism

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: rs933394; hg19: chr19-5269031;