1-29258624-C-T

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_133178.4(PTPRU):c.325C>T(p.Arg109Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,614,124 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

PTPRU
NM_133178.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.613

Variant links:

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]

PTPRU links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 40 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRU	NM_133178.4 link	c.325C>T	p.Arg109Trp	missense_variant	Exon 3 of 30	ENST00000373779.8	NP_573439.2	Q92729-2
PTPRU	NM_005704.5 link	c.325C>T	p.Arg109Trp	missense_variant	Exon 3 of 31		NP_005695.3	Q92729-1
PTPRU	NM_133177.4 link	c.325C>T	p.Arg109Trp	missense_variant	Exon 3 of 31		NP_573438.3	Q92729-4
PTPRU	NM_001195001.2 link	c.325C>T	p.Arg109Trp	missense_variant	Exon 3 of 30		NP_001181930.1	Q92729-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PTPRU	ENST00000373779.8 link	c.325C>T	p.Arg109Trp	missense_variant	Exon 3 of 30	1	NM_133178.4	ENSP00000362884.3	Q92729-2
PTPRU	ENST00000345512.7 link	c.325C>T	p.Arg109Trp	missense_variant	Exon 3 of 31	1		ENSP00000334941.5	Q92729-1
PTPRU	ENST00000460170.2 link	c.325C>T	p.Arg109Trp	missense_variant	Exon 3 of 31	1		ENSP00000432906.1	Q92729-4
PTPRU	ENST00000428026.6 link	c.325C>T	p.Arg109Trp	missense_variant	Exon 3 of 30	1		ENSP00000392332.2	Q92729-3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251408

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000274

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000243

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.0000189

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.325C>T (p.R109W) alteration is located in exon 3 (coding exon 3) of the PTPRU gene. This alteration results from a C to T substitution at nucleotide position 325, causing the arginine (R) at amino acid position 109 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

T;.;.;.

Eigen

Benign

0.15

Eigen_PC

Benign

0.060

FATHMM_MKL

Uncertain

0.76

LIST_S2

Uncertain

0.94

D;D;D;D

M_CAP

Benign

0.059

MetaRNN

Uncertain

0.44

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

M;M;M;M

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-4.3

D;D;D;D

REVEL

Uncertain

0.33

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Pathogenic

0.0010

D;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.51

MVP

0.48

MPC

0.91

ClinPred

0.98

GERP RS

0.38

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.78

gMVP

0.65

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over