rs2319404

Positions:

• chr1-29294375-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133178.4(PTPRU):​c.2476+2349A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,096 control chromosomes in the GnomAD database, including 9,604 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 0.31 (9604 hom., cov: 33)
• Consequence: PTPRU NM_133178.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

Genes affected

PTPRU (HGNC:9683): (protein tyrosine phosphatase receptor type U) 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 possesses an extracellular region, a single transmembrane region, and two tandem intracellular catalytic domains, and thus represents a receptor-type PTP. The extracellular region contains a meprin-A5 antigen-PTP (MAM) domain, Ig-like and fibronectin type III-like repeats. This PTP was thought to play roles in cell-cell recognition and adhesion. Studies of the similar gene in mice suggested the role of this PTP in early neural development. The expression of this gene was reported to be regulated by phorbol myristate acetate (PMA) or calcium ionophore in Jurkat T lymphoma cells. Alternatively spliced transcript variants have been reported. [provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRU	NM_133178.4	c.2476+2349A>G		intron_variant		ENST00000373779.8	NP_573439.2
PTPRU	NM_001195001.2	c.2476+2349A>G		intron_variant			NP_001181930.1
PTPRU	NM_005704.5	c.2506+2349A>G		intron_variant			NP_005695.3
PTPRU	NM_133177.4	c.2476+2349A>G		intron_variant			NP_573438.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRU	ENST00000373779.8	c.2476+2349A>G		intron_variant		1	NM_133178.4	ENSP00000362884	A1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47845 AN: 151978 Hom.: 9585 Cov.: 33

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.315 AC: 47910 AN: 152096 Hom.: 9604 Cov.: 33 AF XY: 0.321 AC XY: 23868 AN XY: 74360

Gnomad4 AFR AF: 0.527

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.639

Gnomad4 SAS AF: 0.436

Gnomad4 FIN AF: 0.208

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.307

Alfa AF: 0.230 Hom.: 2543

Bravo AF: 0.334

Asia WGS AF: 0.506 AC: 1759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.48
DANN	Benign	0.55

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: rs2319404; hg19: chr1-29620887;