1-29294244-C-T

Variant names:

• chr1-29294244-C-T
• rs2319403
• NM_133178.4:c.2476+2218C>T

Variant summary

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

The NM_133178.4(PTPRU):​c.2476+2218C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,042 control chromosomes in the GnomAD database, including 7,568 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 0.29 (7568 hom., cov: 33)
• Consequence: PTPRU NM_133178.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.583
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRU	NM_133178.4	c.2476+2218C>T		intron_variant	Intron 15 of 29	ENST00000373779.8	NP_573439.2
PTPRU	NM_005704.5	c.2506+2218C>T		intron_variant	Intron 16 of 30		NP_005695.3
PTPRU	NM_133177.4	c.2476+2218C>T		intron_variant	Intron 15 of 30		NP_573438.3
PTPRU	NM_001195001.2	c.2476+2218C>T		intron_variant	Intron 15 of 29		NP_001181930.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRU	ENST00000373779.8	c.2476+2218C>T		intron_variant	Intron 15 of 29	1	NM_133178.4	ENSP00000362884.3

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43599 AN: 151924 Hom.: 7553 Cov.: 33

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.287 AC: 43656 AN: 152042 Hom.: 7568 Cov.: 33 AF XY: 0.294 AC XY: 21859 AN XY: 74338

African (AFR) AF: 0.430 AC: 17817 AN: 41428

American (AMR) AF: 0.334 AC: 5096 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 764 AN: 3466

East Asian (EAS) AF: 0.638 AC: 3305 AN: 5180

South Asian (SAS) AF: 0.436 AC: 2101 AN: 4822

European-Finnish (FIN) AF: 0.208 AC: 2196 AN: 10568

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11577 AN: 67980

Other (OTH) AF: 0.289 AC: 611 AN: 2114

Alfa AF: 0.175 Hom.: 542

Bravo AF: 0.303

Asia WGS AF: 0.501 AC: 1741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	13
DANN	Benign	0.92
PhyloP100		0.58
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: rs2319403; hg19: chr1-29620756;