rs9426315

chr1-29298863-G-Achr1-29298863-G-C

Variant summary

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

The NM_133178.4(PTPRU):c.2477-4992G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 152,032 control chromosomes in the GnomAD database, including 26,250 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 0.55 (26250 hom., cov: 32)
• Consequence: PTPRU NM_133178.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

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 (AFR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRU	NM_133178.4	c.2477-4992G>A		intron_variant		ENST00000373779.8
PTPRU	NM_001195001.2	c.2477-4992G>A		intron_variant
PTPRU	NM_005704.5	c.2507-4992G>A		intron_variant
PTPRU	NM_133177.4	c.2477-4992G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRU	ENST00000373779.8	c.2477-4992G>A		intron_variant		1	NM_133178.4	A1

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83425 AN: 151914 Hom.: 26196 Cov.: 32

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.808

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.549 AC: 83536 AN: 152032 Hom.: 26250 Cov.: 32 AF XY: 0.550 AC XY: 40900 AN XY: 74318

Gnomad4 AFR AF: 0.848

Gnomad4 AMR AF: 0.580

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.808

Gnomad4 SAS AF: 0.574

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.549

Alfa AF: 0.525 Hom.: 3610

Bravo AF: 0.582

Asia WGS AF: 0.699 AC: 2432 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	0.055
Dann	Benign	0.47

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: rs9426315; hg19: chr1-29625375; COSMIC: COSV60524127;