chr19-5274373-C-T

Variant names:

• chr19-5274373-C-T
• rs1034917
• NM_002850.4:c.92-29G>A

Variant summary

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

The NM_002850.4(PTPRS):​c.92-29G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,592,672 control chromosomes in the GnomAD database, including 16,234 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 0.15 (1818 hom., cov: 32)
  • Exomes 𝑓: 0.14 (14416 hom.)
• Consequence: PTPRS NM_002850.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 11 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRS	NM_002850.4	c.92-29G>A		intron_variant	Intron 2 of 37	ENST00000262963.11	NP_002841.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRS	ENST00000262963.11	c.92-29G>A		intron_variant	Intron 2 of 37	5	NM_002850.4	ENSP00000262963.8

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22368 AN: 151554 Hom.: 1811 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.0883

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.122

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.150

GnomAD2 exomes AF: 0.156 AC: 37601 AN: 240264 AF XY: 0.151

Gnomad AFR exome AF: 0.160

Gnomad AMR exome AF: 0.307

Gnomad ASJ exome AF: 0.0919

Gnomad EAS exome AF: 0.105

Gnomad FIN exome AF: 0.109

Gnomad NFE exome AF: 0.135

Gnomad OTH exome AF: 0.151

GnomAD4 exome AF: 0.136 AC: 195752 AN: 1441000 Hom.: 14416 Cov.: 32 AF XY: 0.136 AC XY: 96681 AN XY: 713392

African (AFR) AF: 0.161 AC: 5324 AN: 33016

American (AMR) AF: 0.297 AC: 13023 AN: 43786

Ashkenazi Jewish (ASJ) AF: 0.0891 AC: 2288 AN: 25676

East Asian (EAS) AF: 0.0997 AC: 3888 AN: 39008

South Asian (SAS) AF: 0.149 AC: 12684 AN: 85002

European-Finnish (FIN) AF: 0.107 AC: 5618 AN: 52614

Middle Eastern (MID) AF: 0.129 AC: 733 AN: 5680

European-Non Finnish (NFE) AF: 0.132 AC: 144283 AN: 1096844

Other (OTH) AF: 0.133 AC: 7911 AN: 59374

GnomAD4 genome AF: 0.148 AC: 22397 AN: 151672 Hom.: 1818 Cov.: 32 AF XY: 0.148 AC XY: 10999 AN XY: 74114

African (AFR) AF: 0.158 AC: 6523 AN: 41312

American (AMR) AF: 0.245 AC: 3729 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.0883 AC: 306 AN: 3466

East Asian (EAS) AF: 0.111 AC: 572 AN: 5146

South Asian (SAS) AF: 0.144 AC: 692 AN: 4802

European-Finnish (FIN) AF: 0.106 AC: 1113 AN: 10538

Middle Eastern (MID) AF: 0.107 AC: 31 AN: 290

European-Non Finnish (NFE) AF: 0.132 AC: 8987 AN: 67874

Other (OTH) AF: 0.153 AC: 322 AN: 2102

Alfa AF: 0.134 Hom.: 4112

Bravo AF: 0.157

Asia WGS AF: 0.145 AC: 506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.27
DANN	Benign	0.67
PhyloP100		-1.3
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: rs1034917; hg19: chr19-5274384;