rs7963963

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.5075T>C(p.Ile1692Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0309 in 1,545,564 control chromosomes in the GnomAD database, including 2,365 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. I1692I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.079 ( 1150 hom., cov: 32)

Exomes 𝑓: 0.026 ( 1215 hom. )

Consequence

PTPRQ
NM_001145026.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.55

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

PTPRQ links:

ENSG00000304204 (HGNC:):

ENSG00000304204 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=0.0016589165).

BP6

Variant 12-80613748-T-C is Benign according to our data. Variant chr12-80613748-T-C is described in ClinVar as Benign. ClinVar VariationId is 586389.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.224 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRQ	NM_001145026.2	MANE Select	c.5075T>C	p.Ile1692Thr	missense	Exon 29 of 45	NP_001138498.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PTPRQ	ENST00000644991.3	MANE Select	c.5075T>C	p.Ile1692Thr	missense	Exon 29 of 45	ENSP00000495607.1
PTPRQ	ENST00000616559.4	TSL:5	c.5201T>C	p.Ile1734Thr	missense	Exon 30 of 45	ENSP00000483259.1
ENSG00000304204	ENST00000801015.1		n.101-33339A>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0791

AC:

11886

AN:

150318

Hom.:

1144

Cov.:

show subpopulations

Gnomad AFR

AF:

0.228

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0334

Gnomad ASJ

AF:

0.0345

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.0123

Gnomad FIN

AF:

0.0184

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0229

Gnomad OTH

AF:

0.0572

GnomAD2 exomes

AF:

0.0296

AC:

4510

AN:

152480

AF XY:

0.0265

show subpopulations

Gnomad AFR exome

AF:

0.230

Gnomad AMR exome

AF:

0.0183

Gnomad ASJ exome

AF:

0.0326

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0196

Gnomad NFE exome

AF:

0.0223

Gnomad OTH exome

AF:

0.0216

GnomAD4 exome

AF:

0.0257

AC:

35795

AN:

1395128

Hom.:

1215

Cov.:

AF XY:

0.0249

AC XY:

17134

AN XY:

688104

show subpopulations

African (AFR)

AF:

0.231

AC:

7207

AN:

31248

American (AMR)

AF:

0.0212

AC:

755

AN:

35642

Ashkenazi Jewish (ASJ)

AF:

0.0333

AC:

832

AN:

24984

East Asian (EAS)

AF:

0.00

AC:

AN:

35590

South Asian (SAS)

AF:

0.0139

AC:

1101

AN:

78998

European-Finnish (FIN)

AF:

0.0194

AC:

954

AN:

49254

Middle Eastern (MID)

AF:

0.0186

AC:

105

AN:

5656

European-Non Finnish (NFE)

AF:

0.0213

AC:

22950

AN:

1076050

Other (OTH)

AF:

0.0328

AC:

1891

AN:

57706

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

1883

3765

5648

7530

9413

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

972

1944

2916

3888

4860

<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:

0.0792

AC:

11919

AN:

150436

Hom.:

1150

Cov.:

AF XY:

0.0767

AC XY:

5638

AN XY:

73506

show subpopulations

African (AFR)

AF:

0.228

AC:

9385

AN:

41220

American (AMR)

AF:

0.0333

AC:

501

AN:

15030

Ashkenazi Jewish (ASJ)

AF:

0.0345

AC:

118

AN:

3424

East Asian (EAS)

AF:

0.000196

AC:

AN:

5112

South Asian (SAS)

AF:

0.0123

AC:

AN:

4780

European-Finnish (FIN)

AF:

0.0184

AC:

195

AN:

10612

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0230

AC:

1537

AN:

66966

Other (OTH)

AF:

0.0566

AC:

118

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

462

924

1385

1847

2309

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

122

244

366

488

610

<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:

0.0376

Hom.:

1491

Bravo

AF:

0.0864

TwinsUK

AF:

0.0227

AC:

ALSPAC

AF:

0.0234

AC:

ESP6500AA

AF:

0.223

AC:

309

ESP6500EA

AF:

0.0267

AC:

ExAC

AF:

0.0391

AC:

851

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.018

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.89

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.1

PhyloP100

4.5

PrimateAI

Uncertain

0.56

Sift4G

Uncertain

0.0040

Vest4

0.28

ClinPred

0.024

GERP RS

6.0

gMVP

0.15

Mutation Taster

=92/8

polymorphism (auto)

(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

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

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over