Genetic Variant PTPRR:p.Lys314Ile (chr12-70745884-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002849.4(PTPRR):c.941A>T(p.Lys314Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 30)

Failed GnomAD Quality Control

Consequence

PTPRR
NM_002849.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.831

Publications

43 publications found

Variant links:

Genes affected

PTPRR (HGNC:9680): (protein tyrosine phosphatase receptor type R) 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 a single intracellular catalytic domain, and thus represents a receptor-type PTP. Silencing of this gene has been associated with colorectal cancer. Multiple transcript variants encoding different isoforms have been found for this gene. This gene shares a symbol (PTPRQ) with another gene, protein tyrosine phosphatase, receptor type, Q (GeneID 374462), which is also located on chromosome 12. [provided by RefSeq, May 2011]

PTPRR links:

ENSG00000307941 (HGNC:):

ENSG00000307941 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1787681).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002849.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PTPRR	NM_002849.4	MANE Select	c.941A>T	p.Lys314Ile	missense	Exon 6 of 14	NP_002840.2
PTPRR	NM_001207015.2		c.605A>T	p.Lys202Ile	missense	Exon 5 of 13	NP_001193944.1
PTPRR	NM_001207016.1		c.323A>T	p.Lys108Ile	missense	Exon 3 of 11	NP_001193945.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PTPRR	ENST00000283228.7	TSL:1 MANE Select	c.941A>T	p.Lys314Ile	missense	Exon 6 of 14	ENSP00000283228.2
PTPRR	ENST00000378778.5	TSL:1	c.323A>T	p.Lys108Ile	missense	Exon 3 of 11	ENSP00000368054.1
PTPRR	ENST00000440835.6	TSL:1	c.206A>T	p.Lys69Ile	missense	Exon 2 of 10	ENSP00000391750.2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151908

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

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

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

151908

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74158

African (AFR)

AF:

0.00

AC:

AN:

41292

American (AMR)

AF:

0.00

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67998

Other (OTH)

AF:

0.00

AC:

AN:

2086

Alfa

AF:

0.00

Hom.:

197752

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.29

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.81

M_CAP

Benign

0.019

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.0

PhyloP100

0.83

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.72

REVEL

Benign

0.13

Sift

Benign

0.059

Sift4G

Benign

0.17

Polyphen

0.25

Vest4

0.59

MutPred

0.42

Gain of sheet (P = 0.0036)

MVP

0.59

MPC

0.38

ClinPred

0.63

GERP RS

0.59

Varity_R

0.13

gMVP

0.42

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over