1-29258717-G-A

Position:

chr1-29258717-G-A

Variant summary

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

The NM_133178.4(PTPRU):c.418G>A(p.Gly140Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000232 in 1,609,554 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

PTPRU
NM_133178.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 10.0

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 GnomAd4 at 35 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRU	NM_133178.4 linkuse as main transcript	c.418G>A	p.Gly140Ser	missense_variant	3/30	ENST00000373779.8	NP_573439.2	Q92729-2
PTPRU	NM_005704.5 linkuse as main transcript	c.418G>A	p.Gly140Ser	missense_variant	3/31		NP_005695.3	Q92729-1
PTPRU	NM_133177.4 linkuse as main transcript	c.418G>A	p.Gly140Ser	missense_variant	3/31		NP_573438.3	Q92729-4
PTPRU	NM_001195001.2 linkuse as main transcript	c.418G>A	p.Gly140Ser	missense_variant	3/30		NP_001181930.1	Q92729-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PTPRU	ENST00000373779.8 linkuse as main transcript	c.418G>A	p.Gly140Ser	missense_variant	3/30	1	NM_133178.4	ENSP00000362884.3	Q92729-2
PTPRU	ENST00000345512.7 linkuse as main transcript	c.418G>A	p.Gly140Ser	missense_variant	3/31	1		ENSP00000334941.5	Q92729-1
PTPRU	ENST00000460170.2 linkuse as main transcript	c.418G>A	p.Gly140Ser	missense_variant	3/31	1		ENSP00000432906.1	Q92729-4
PTPRU	ENST00000428026.6 linkuse as main transcript	c.418G>A	p.Gly140Ser	missense_variant	3/30	1		ENSP00000392332.2	Q92729-3

Frequencies

GnomAD3 genomes

AF:

0.000236

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000411

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000134

AC:

AN:

246230

Hom.:

AF XY:

0.000150

AC XY:

AN XY:

133144

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.0000296

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000333

Gnomad FIN exome

AF:

0.000187

Gnomad NFE exome

AF:

0.000225

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000232

AC:

338

AN:

1457208

Hom.:

Cov.:

AF XY:

0.000237

AC XY:

172

AN XY:

724452

show subpopulations

Gnomad4 AFR exome

AF:

0.000210

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.0000388

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000282

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000230

AC:

AN:

152346

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000336

Hom.:

Bravo

AF:

0.000215

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000107

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 13, 2023

The c.418G>A (p.G140S) alteration is located in exon 3 (coding exon 3) of the PTPRU gene. This alteration results from a G to A substitution at nucleotide position 418, causing the glycine (G) at amino acid position 140 to be replaced by a serine (S). 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

0.12

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.069

T;.;.;.

Eigen

Pathogenic

0.91

Eigen_PC

Pathogenic

0.89

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

D;D;D;D

M_CAP

Benign

0.0086

MetaRNN

Uncertain

0.44

T;T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.6

M;M;M;M

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.2

N;N;N;N

REVEL

Uncertain

0.33

Sift

Benign

0.11

T;T;T;T

Sift4G

Benign

0.086

T;T;T;T

Polyphen

1.0

D;D;D;D

Vest4

0.69

MVP

0.57

MPC

0.86

ClinPred

0.20

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.66

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