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
• Publications: 8 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.574 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.3765+147A>G		intron	N/A	NP_002841.3
	PTPRS	NM_001394011.1		c.3699+147A>G		intron	N/A	NP_001380940.1
	PTPRS	NM_001394012.1		c.3726+147A>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.3765+147A>G		intron	N/A	ENSP00000262963.8
	PTPRS	ENST00000587303.5	TSL:1	c.3765+147A>G		intron	N/A	ENSP00000467537.1
	PTPRS	ENST00000588012.5	TSL:1	c.3699+147A>G		intron	N/A	ENSP00000465443.1

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

African (AFR) AF: 0.214 AC: 4127 AN: 19306

American (AMR) AF: 0.340 AC: 8461 AN: 24902

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 5467 AN: 16266

East Asian (EAS) AF: 0.573 AC: 20386 AN: 35594

South Asian (SAS) AF: 0.455 AC: 25534 AN: 56126

European-Finnish (FIN) AF: 0.375 AC: 13651 AN: 36450

Middle Eastern (MID) AF: 0.365 AC: 969 AN: 2652

European-Non Finnish (NFE) AF: 0.430 AC: 243241 AN: 565580

Other (OTH) 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

African (AFR) AF: 0.221 AC: 9172 AN: 41514

American (AMR) AF: 0.326 AC: 4979 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1222 AN: 3468

East Asian (EAS) AF: 0.592 AC: 3043 AN: 5142

South Asian (SAS) AF: 0.443 AC: 2126 AN: 4804

European-Finnish (FIN) AF: 0.377 AC: 3993 AN: 10580

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28917 AN: 67950

Other (OTH) AF: 0.355 AC: 749 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.65
PhyloP100		-0.73
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: rs12975955; hg19: chr19-5219803;