chr19-5219792-T-C

Variant names:

• chr19-5219792-T-C
• rs12975955
• NM_002850.4:c.3765+147A>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.3765+147A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 946,482 control chromosomes in the GnomAD database, including 83,859 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 0.36 (10554 hom., cov: 33)
  • Exomes 𝑓: 0.42 (73305 hom.)
• Consequence: PTPRS NM_002850.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.727

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRS	NM_002850.4	c.3765+147A>G		intron_variant	Intron 22 of 37	ENST00000262963.11	NP_002841.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRS	ENST00000262963.11	c.3765+147A>G		intron_variant	Intron 22 of 37	5	NM_002850.4	ENSP00000262963.8

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54672 AN: 151914 Hom.: 10550 Cov.: 33

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.353

GnomAD4 exome AF: 0.424 AC: 336818 AN: 794450 Hom.: 73305 AF XY: 0.425 AC XY: 171926 AN XY: 404400

Gnomad4 AFR exome AF: 0.214 AC: 4127 AN: 19306

Gnomad4 AMR exome AF: 0.340 AC: 8461 AN: 24902

Gnomad4 ASJ exome AF: 0.336 AC: 5467 AN: 16266

Gnomad4 EAS exome AF: 0.573 AC: 20386 AN: 35594

Gnomad4 SAS exome AF: 0.455 AC: 25534 AN: 56126

Gnomad4 FIN exome AF: 0.375 AC: 13651 AN: 36450

Gnomad4 NFE exome AF: 0.430 AC: 243241 AN: 565580

Gnomad4 Remaining exome AF: 0.399 AC: 14982 AN: 37574

GnomAD4 genome AF: 0.360 AC: 54697 AN: 152032 Hom.: 10554 Cov.: 33 AF XY: 0.360 AC XY: 26745 AN XY: 74298

Gnomad4 AFR AF: 0.221 AC: 0.220938 AN: 0.220938

Gnomad4 AMR AF: 0.326 AC: 0.326321 AN: 0.326321

Gnomad4 ASJ AF: 0.352 AC: 0.352364 AN: 0.352364

Gnomad4 EAS AF: 0.592 AC: 0.591793 AN: 0.591793

Gnomad4 SAS AF: 0.443 AC: 0.442548 AN: 0.442548

Gnomad4 FIN AF: 0.377 AC: 0.37741 AN: 0.37741

Gnomad4 NFE AF: 0.426 AC: 0.425563 AN: 0.425563

Gnomad4 OTH AF: 0.355 AC: 0.35464 AN: 0.35464

Alfa AF: 0.409 Hom.: 6683

Bravo AF: 0.352

Asia WGS AF: 0.436 AC: 1519 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.65
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

Publications

LitVar

Other links and lift over

dbSNP: rs12975955; hg19: chr19-5219803;