Genetic Variant PTPRQ:c.6192+513T>C (chr12-80658574-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001145026.2(PTPRQ):c.6192+513T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 151,836 control chromosomes in the GnomAD database, including 22,128 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.50 ( 22128 hom., cov: 31)

Consequence

PTPRQ
NM_001145026.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.681

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRQ	NM_001145026.2 link	c.6192+513T>C		intron_variant	Intron 39 of 44	ENST00000644991.3	NP_001138498.1
LOC105369867	XR_007063388.1 link	n.130+48535A>G		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
PTPRQ	ENST00000644991.3 link	c.6192+513T>C	intron_variant	Intron 39 of 44		NM_001145026.2	ENSP00000495607.1
PTPRQ	ENST00000616559.4 link	c.6291+513T>C	intron_variant	Intron 39 of 44	5		ENSP00000483259.1
ENSG00000304204	ENST00000801015.1 link	n.100+48535A>G	intron_variant	Intron 1 of 2
ENSG00000304204	ENST00000801016.1 link	n.101-6223A>G	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.501

AC:

76072

AN:

151718

Hom.:

22083

Cov.:

show subpopulations

Gnomad AFR

AF:

0.812

Gnomad AMI

AF:

0.533

Gnomad AMR

AF:

0.394

Gnomad ASJ

AF:

0.379

Gnomad EAS

AF:

0.471

Gnomad SAS

AF:

0.478

Gnomad FIN

AF:

0.329

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.375

Gnomad OTH

AF:

0.453

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.502

AC:

76173

AN:

151836

Hom.:

22128

Cov.:

AF XY:

0.497

AC XY:

36869

AN XY:

74212

show subpopulations

African (AFR)

AF:

0.812

AC:

33676

AN:

41454

American (AMR)

AF:

0.394

AC:

5986

AN:

15204

Ashkenazi Jewish (ASJ)

AF:

0.379

AC:

1313

AN:

3460

East Asian (EAS)

AF:

0.471

AC:

2432

AN:

5160

South Asian (SAS)

AF:

0.480

AC:

2310

AN:

4816

European-Finnish (FIN)

AF:

0.329

AC:

3478

AN:

10576

Middle Eastern (MID)

AF:

0.347

AC:

102

AN:

294

European-Non Finnish (NFE)

AF:

0.375

AC:

25442

AN:

67854

Other (OTH)

AF:

0.450

AC:

948

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1628

3256

4885

6513

8141

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

640

1280

1920

2560

3200

<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:

0.393

Hom.:

19489

Bravo

AF:

0.516

Asia WGS

AF:

0.502

AC:

1747

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

1.3

(source)

DANN

Benign

0.74

PhyloP100

-0.68

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over