12-80670365-C-T

Variant names:

Variant summary

Our verdict is Pathogenic. The variant received 17 ACMG points: 17P and 0B. PVS1PP3PP5_Very_Strong

The NM_001145026.2(PTPRQ):c.6475C>T(p.Arg2159*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000029 in 1,550,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

PTPRQ
NM_001145026.2 stop_gained

Scores

Clinical Significance

Pathogenic criteria provided, multiple submitters, no conflicts P:4

Conservation

PhyloP100: 0.939

Publications

1 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: Pathogenic. The variant received 17 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

PP5

Variant 12-80670365-C-T is Pathogenic according to our data. Variant chr12-80670365-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 523416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.6475C>T	p.Arg2159*	stop_gained	Exon 42 of 45	NP_001138498.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PTPRQ	ENST00000644991.3	MANE Select	c.6475C>T	p.Arg2159*	stop_gained	Exon 42 of 45	ENSP00000495607.1
PTPRQ	ENST00000616559.4	TSL:5	c.6574C>T	p.Arg2192*	stop_gained	Exon 42 of 45	ENSP00000483259.1
ENSG00000304204	ENST00000801015.1		n.100+36744G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151956

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000320

AC:

AN:

156260

AF XY:

0.0000242

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000827

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000293

AC:

AN:

1398606

Hom.:

Cov.:

AF XY:

0.0000319

AC XY:

AN XY:

689816

show subpopulations

African (AFR)

AF:

0.0000317

AC:

AN:

31526

American (AMR)

AF:

0.00

AC:

AN:

35652

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25150

East Asian (EAS)

AF:

0.00

AC:

AN:

35720

South Asian (SAS)

AF:

0.00

AC:

AN:

79162

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49288

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

0.0000343

AC:

AN:

1078442

Other (OTH)

AF:

0.0000517

AC:

AN:

57978

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000263

AC:

AN:

151956

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74188

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41390

American (AMR)

AF:

0.00

AC:

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.000194

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67984

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.588

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000434

Hom.:

Bravo

AF:

0.0000151

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Pathogenic:3

Mar 14, 2025

GeneDx

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 23208854, 32860223, 36147510, 34335733)

Feb 01, 2021

Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PTPRQ: PVS1, PM3:Strong, PM2

Pes planus;C0030193:Pain;C0231686:Unsteady gait;C0728829:Pes cavus;C1384666:Hearing impairment;C1836843:Loss of ambulation;C1849134:Impaired vibration sensation in the lower limbs

Pathogenic:1

Jan 01, 2017

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Pathogenic

0.29

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.28

Eigen_PC

Benign

0.051

FATHMM_MKL

Benign

0.41

PhyloP100

0.94

Vest4

0.43

GERP RS

1.7

Mutation Taster

=42/158

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.53

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.53

Position offset: -21

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over