12-80444784-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001145026.2(PTPRQ):c.98C>T(p.Thr33Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0263 in 1,539,526 control chromosomes in the GnomAD database, including 957 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 131 hom., cov: 32)

Exomes 𝑓: 0.026 ( 826 hom. )

Consequence

PTPRQ
NM_001145026.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.11

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive nonsyndromic hearing loss 84A
Inheritance: AR, SD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
hearing loss, autosomal recessive
Inheritance: Unknown, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hearing loss, autosomal dominant 73
Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

PTPRQ links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025488138).

BP6

Variant 12-80444784-C-T is Benign according to our data. Variant chr12-80444784-C-T is described in ClinVar as Benign. ClinVar VariationId is 508621.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0804 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145026.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRQ	NM_001145026.2	MANE Select	c.98C>T	p.Thr33Ile	missense	Exon 2 of 45	NP_001138498.1	A0A087WZU1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTPRQ	ENST00000644991.3	MANE Select	c.98C>T	p.Thr33Ile	missense	Exon 2 of 45	ENSP00000495607.1	A0A087WZU1
PTPRQ	ENST00000616559.4	TSL:5	c.224C>T	p.Thr75Ile	missense	Exon 3 of 45	ENSP00000483259.1	A0A087X0B9
PTPRQ	ENST00000547376.5	TSL:5	c.962C>T	p.Thr321Ile	missense	Exon 11 of 12	ENSP00000448844.1	F8VXI2

Frequencies

GnomAD3 genomes

AF:

0.0322

AC:

4885

AN:

151738

Hom.:

130

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0323

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0759

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.0541

Gnomad SAS

AF:

0.0870

Gnomad FIN

AF:

0.0337

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0183

Gnomad OTH

AF:

0.0206

GnomAD2 exomes

AF:

0.0456

AC:

6999

AN:

153410

AF XY:

0.0466

show subpopulations

Gnomad AFR exome

AF:

0.0382

Gnomad AMR exome

AF:

0.0944

Gnomad ASJ exome

AF:

0.0136

Gnomad EAS exome

AF:

0.0513

Gnomad FIN exome

AF:

0.0340

Gnomad NFE exome

AF:

0.0181

Gnomad OTH exome

AF:

0.0322

GnomAD4 exome

AF:

0.0256

AC:

35520

AN:

1387670

Hom.:

826

Cov.:

AF XY:

0.0271

AC XY:

18554

AN XY:

684630

show subpopulations

African (AFR)

AF:

0.0315

AC:

980

AN:

31160

American (AMR)

AF:

0.0912

AC:

3232

AN:

35456

Ashkenazi Jewish (ASJ)

AF:

0.0140

AC:

346

AN:

24732

East Asian (EAS)

AF:

0.0560

AC:

1970

AN:

35184

South Asian (SAS)

AF:

0.0830

AC:

6526

AN:

78652

European-Finnish (FIN)

AF:

0.0317

AC:

1546

AN:

48782

Middle Eastern (MID)

AF:

0.00878

AC:

AN:

5578

European-Non Finnish (NFE)

AF:

0.0181

AC:

19358

AN:

1070874

Other (OTH)

AF:

0.0264

AC:

1513

AN:

57252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

1605

3209

4814

6418

8023

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

840

1680

2520

3360

4200

<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

AF:

0.0322

AC:

4894

AN:

151856

Hom.:

131

Cov.:

AF XY:

0.0351

AC XY:

2603

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.0324

AC:

1343

AN:

41504

American (AMR)

AF:

0.0759

AC:

1154

AN:

15202

Ashkenazi Jewish (ASJ)

AF:

0.0121

AC:

AN:

3460

East Asian (EAS)

AF:

0.0538

AC:

278

AN:

5166

South Asian (SAS)

AF:

0.0872

AC:

420

AN:

4814

European-Finnish (FIN)

AF:

0.0337

AC:

357

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0183

AC:

1239

AN:

67788

Other (OTH)

AF:

0.0204

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

241

482

724

965

1206

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0214

Hom.:

129

Bravo

AF:

0.0338

TwinsUK

AF:

0.0186

AC:

ALSPAC

AF:

0.0176

AC:

ESP6500AA

AF:

0.0311

AC:

ESP6500EA

AF:

0.0192

AC:

ExAC

AF:

0.0462

AC:

999

Asia WGS

AF:

0.0600

AC:

209

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.055

Eigen

Uncertain

0.34

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.74

MetaRNN

Benign

0.0025

MetaSVM

Benign

-0.75

PhyloP100

4.1

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-3.1

REVEL

Uncertain

0.36

Sift

Uncertain

0.014

Sift4G

Pathogenic

0.0

Vest4

0.17

ClinPred

0.012

GERP RS

4.9

gMVP

0.48

Mutation Taster

=92/8

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over