Genetic Variant NM_133178.4:c.1699G>C (chr1-29279591-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_133178.4(PTPRU):c.1699G>C(p.Val567Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000753 in 1,461,748 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V567M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

PTPRU
NM_133178.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.76

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRU	NM_133178.4 link	c.1699G>C	p.Val567Leu	missense_variant	Exon 10 of 30	ENST00000373779.8	NP_573439.2	Q92729-2
PTPRU	NM_005704.5 link	c.1699G>C	p.Val567Leu	missense_variant	Exon 10 of 31		NP_005695.3	Q92729-1
PTPRU	NM_133177.4 link	c.1699G>C	p.Val567Leu	missense_variant	Exon 10 of 31		NP_573438.3	Q92729-4
PTPRU	NM_001195001.2 link	c.1699G>C	p.Val567Leu	missense_variant	Exon 10 of 30		NP_001181930.1	Q92729-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRU	ENST00000373779.8 link	c.1699G>C	p.Val567Leu	missense_variant	Exon 10 of 30	1	NM_133178.4	ENSP00000362884.3		Q92729-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461748

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727166

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53276

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000989

AC:

AN:

1112012

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.075

T;.;.;.

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.91

D;D;D;D

M_CAP

Benign

0.079

MetaRNN

Uncertain

0.60

D;D;D;D

MetaSVM

Uncertain

-0.15

MutationAssessor

Benign

1.7

L;L;L;L

PhyloP100

6.8

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.1

N;N;N;N

REVEL

Uncertain

0.44

Sift

Benign

0.61

T;T;T;T

Sift4G

Benign

0.17

T;T;T;T

Polyphen

1.0

D;D;D;D

Vest4

0.56

MutPred

0.76

Loss of MoRF binding (P = 0.1069);Loss of MoRF binding (P = 0.1069);Loss of MoRF binding (P = 0.1069);Loss of MoRF binding (P = 0.1069);

MVP

0.79

MPC

1.2

ClinPred

0.98

GERP RS

5.2

Varity_R

0.16

gMVP

0.51

Mutation Taster

=45/55

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over