Variant 12-70745884-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002849.4(PTPRR):c.941A>G(p.Lys314Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 1,613,718 control chromosomes in the GnomAD database, including 480,733 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.68 ( 37704 hom., cov: 30)

Exomes 𝑓: 0.78 ( 443029 hom. )

Consequence

PTPRR
NM_002849.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.831

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:

LOC124902960 (HGNC:):

LOC124902960 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.953038E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRR	NM_002849.4 link	c.941A>G	p.Lys314Arg	missense_variant	6/14	ENST00000283228.7	NP_002840.2	Q15256-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRR	ENST00000283228.7 link	c.941A>G	p.Lys314Arg	missense_variant	6/14	1	NM_002849.4	ENSP00000283228.2		Q15256-1

Frequencies

GnomAD3 genomes

AF:

0.679

AC:

103074

AN:

151840

Hom.:

37680

Cov.:

show subpopulations

Gnomad AFR

AF:

0.376

Gnomad AMI

AF:

0.789

Gnomad AMR

AF:

0.794

Gnomad ASJ

AF:

0.789

Gnomad EAS

AF:

0.923

Gnomad SAS

AF:

0.765

Gnomad FIN

AF:

0.807

Gnomad MID

AF:

0.728

Gnomad NFE

AF:

0.784

Gnomad OTH

AF:

0.708

GnomAD3 exomes

AF:

0.773

AC:

194147

AN:

251102

Hom.:

76815

AF XY:

0.775

AC XY:

105209

AN XY:

135724

show subpopulations

Gnomad AFR exome

AF:

0.362

Gnomad AMR exome

AF:

0.840

Gnomad ASJ exome

AF:

0.788

Gnomad EAS exome

AF:

0.923

Gnomad SAS exome

AF:

0.747

Gnomad FIN exome

AF:

0.811

Gnomad NFE exome

AF:

0.786

Gnomad OTH exome

AF:

0.777

GnomAD4 exome

AF:

0.775

AC:

1132985

AN:

1461762

Hom.:

443029

Cov.:

AF XY:

0.776

AC XY:

563962

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.354

Gnomad4 AMR exome

AF:

0.835

Gnomad4 ASJ exome

AF:

0.783

Gnomad4 EAS exome

AF:

0.924

Gnomad4 SAS exome

AF:

0.750

Gnomad4 FIN exome

AF:

0.808

Gnomad4 NFE exome

AF:

0.782

Gnomad4 OTH exome

AF:

0.755

GnomAD4 genome

AF:

0.679

AC:

103135

AN:

151956

Hom.:

37704

Cov.:

AF XY:

0.684

AC XY:

50772

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.376

Gnomad4 AMR

AF:

0.794

Gnomad4 ASJ

AF:

0.789

Gnomad4 EAS

AF:

0.923

Gnomad4 SAS

AF:

0.765

Gnomad4 FIN

AF:

0.807

Gnomad4 NFE

AF:

0.784

Gnomad4 OTH

AF:

0.712

Alfa

AF:

0.768

Hom.:

111788

Bravo

AF:

0.666

TwinsUK

AF:

0.772

AC:

2862

ALSPAC

AF:

0.775

AC:

2985

ESP6500AA

AF:

0.380

AC:

1674

ESP6500EA

AF:

0.785

AC:

6753

ExAC

AF:

0.762

AC:

92520

Asia WGS

AF:

0.829

AC:

2883

AN:

3478

EpiCase

AF:

0.777

EpiControl

AF:

0.782

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.13

.;.;T;.;.;T

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.60

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.56

.;T;T;T;T;T

MetaRNN

Benign

7.0e-7

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.77

.;.;N;.;.;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.37

N;N;N;N;N;N

REVEL

Benign

0.031

Sift

Benign

0.61

T;T;T;T;T;T

Sift4G

Benign

0.50

T;T;T;T;T;.

Polyphen

0.0

.;B;B;.;.;.

Vest4

0.090

MPC

0.093

ClinPred

0.0023

GERP RS

0.59

Varity_R

0.027

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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