Variant 12-80444395-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001145026.2(PTPRQ):c.50C>T(p.Thr17Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0344 in 1,454,900 control chromosomes in the GnomAD database, including 2,756 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.091 ( 1305 hom., cov: 32)

Exomes 𝑓: 0.028 ( 1451 hom. )

Consequence

PTPRQ
NM_001145026.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.315

Variant links:

Genes affected

PTPRQ (HGNC:9679): (protein tyrosine phosphatase receptor type Q) This locus encodes a member of the type III receptor-like protein-tyrosine phosphatase family. The encoded protein catalyzes the dephosphorylation of phosphotyrosine and phosphatidylinositol and plays roles in cellular proliferation and differentiation. Mutations at this locus have been linked to autosomal recessive deafness. [provided by RefSeq, Mar 2014]

PTPRQ links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002832681).

BP6

Variant 12-80444395-C-T is Benign according to our data. Variant chr12-80444395-C-T is described in ClinVar as [Benign]. Clinvar id is 508618.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-80444395-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRQ	NM_001145026.2 linkuse as main transcript	c.50C>T	p.Thr17Ile	missense_variant	1/45	ENST00000644991.3	NP_001138498.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRQ	ENST00000644991.3 linkuse as main transcript	c.50C>T	p.Thr17Ile	missense_variant	1/45		NM_001145026.2	ENSP00000495607	P2

Frequencies

GnomAD3 genomes

AF:

0.0912

AC:

13807

AN:

151426

Hom.:

1302

Cov.:

show subpopulations

Gnomad AFR

AF:

0.235

Gnomad AMI

AF:

0.0198

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.0257

Gnomad EAS

AF:

0.0539

Gnomad SAS

AF:

0.0877

Gnomad FIN

AF:

0.0336

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0190

Gnomad OTH

AF:

0.0610

GnomAD3 exomes

AF:

0.0571

AC:

8637

AN:

151140

Hom.:

528

AF XY:

0.0558

AC XY:

4482

AN XY:

80312

show subpopulations

Gnomad AFR exome

AF:

0.243

Gnomad AMR exome

AF:

0.102

Gnomad ASJ exome

AF:

0.0250

Gnomad EAS exome

AF:

0.0480

Gnomad SAS exome

AF:

0.0832

Gnomad FIN exome

AF:

0.0335

Gnomad NFE exome

AF:

0.0185

Gnomad OTH exome

AF:

0.0380

GnomAD4 exome

AF:

0.0278

AC:

36261

AN:

1303356

Hom.:

1451

Cov.:

AF XY:

0.0290

AC XY:

18753

AN XY:

647394

show subpopulations

Gnomad4 AFR exome

AF:

0.215

Gnomad4 AMR exome

AF:

0.100

Gnomad4 ASJ exome

AF:

0.0242

Gnomad4 EAS exome

AF:

0.0552

Gnomad4 SAS exome

AF:

0.0776

Gnomad4 FIN exome

AF:

0.0314

Gnomad4 NFE exome

AF:

0.0149

Gnomad4 OTH exome

AF:

0.0352

GnomAD4 genome

AF:

0.0912

AC:

13828

AN:

151544

Hom.:

1305

Cov.:

AF XY:

0.0907

AC XY:

6719

AN XY:

74060

show subpopulations

Gnomad4 AFR

AF:

0.235

Gnomad4 AMR

AF:

0.102

Gnomad4 ASJ

AF:

0.0257

Gnomad4 EAS

AF:

0.0536

Gnomad4 SAS

AF:

0.0879

Gnomad4 FIN

AF:

0.0336

Gnomad4 NFE

AF:

0.0190

Gnomad4 OTH

AF:

0.0604

Alfa

AF:

0.0334

Hom.:

452

Bravo

AF:

0.101

TwinsUK

AF:

0.0189

AC:

ALSPAC

AF:

0.0184

AC:

ExAC

AF:

0.0708

AC:

1510

Asia WGS

AF:

0.0700

AC:

247

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Dec 06, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 09, 2017

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.93

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.42

.;T

MetaRNN

Benign

0.0028

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.42

Sift4G

Benign

0.27

T;.

Vest4

0.031

ClinPred

0.0052

GERP RS

3.9

gMVP

0.14

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over