Variant rs370586274 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_133178.4(PTPRU):c.615C>G(p.Asn205Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,882 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N205N) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PTPRU
NM_133178.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.61

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRU	NM_133178.4 link	c.615C>G	p.Asn205Lys	missense_variant	Exon 5 of 30	ENST00000373779.8	NP_573439.2	Q92729-2
PTPRU	NM_005704.5 link	c.615C>G	p.Asn205Lys	missense_variant	Exon 5 of 31		NP_005695.3	Q92729-1
PTPRU	NM_133177.4 link	c.615C>G	p.Asn205Lys	missense_variant	Exon 5 of 31		NP_573438.3	Q92729-4
PTPRU	NM_001195001.2 link	c.615C>G	p.Asn205Lys	missense_variant	Exon 5 of 30		NP_001181930.1	Q92729-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PTPRU	ENST00000373779.8 link	c.615C>G	p.Asn205Lys	missense_variant	Exon 5 of 30	1	NM_133178.4	ENSP00000362884.3	Q92729-2
PTPRU	ENST00000345512.7 link	c.615C>G	p.Asn205Lys	missense_variant	Exon 5 of 31	1		ENSP00000334941.5	Q92729-1
PTPRU	ENST00000460170.2 link	c.615C>G	p.Asn205Lys	missense_variant	Exon 5 of 31	1		ENSP00000432906.1	Q92729-4
PTPRU	ENST00000428026.6 link	c.615C>G	p.Asn205Lys	missense_variant	Exon 5 of 30	1		ENSP00000392332.2	Q92729-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000404

AC:

AN:

247468

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134578

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000899

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1453882

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723062

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.03e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.78

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

T;.;.;.

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.22

LIST_S2

Uncertain

0.95

D;D;D;D

M_CAP

Uncertain

0.10

MetaRNN

Uncertain

0.60

D;D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

M;M;M;M

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-3.1

D;D;D;D

REVEL

Benign

0.14

Sift

Uncertain

0.018

D;D;D;D

Sift4G

Uncertain

0.030

D;D;D;D

Polyphen

0.44

B;P;P;P

Vest4

0.94

MutPred

0.44

Gain of ubiquitination at N205 (P = 0.0219);Gain of ubiquitination at N205 (P = 0.0219);Gain of ubiquitination at N205 (P = 0.0219);Gain of ubiquitination at N205 (P = 0.0219);

MVP

0.26

MPC

1.4

ClinPred

0.88

GERP RS

-4.5

Varity_R

0.24

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over