Genetic Variant PTPRQ:c.3874-519G>A (chr12-80546037-G-A) – 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.3874-519G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0205 in 152,128 control chromosomes in the GnomAD database, including 104 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 0.021 ( 104 hom., cov: 32)

Consequence

PTPRQ
NM_001145026.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.365

Publications

0 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:

LOC105369867 (HGNC:):

LOC105369867 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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRQ	NM_001145026.2 link	c.3874-519G>A		intron_variant	Intron 23 of 44	ENST00000644991.3	NP_001138498.1	A0A087WZU1
LOC105369867	XR_007063388.1 link	n.415+4591C>T		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PTPRQ	ENST00000644991.3 link	c.3874-519G>A	intron_variant	Intron 23 of 44		NM_001145026.2	ENSP00000495607.1	A0A087WZU1
PTPRQ	ENST00000616559.4 link	c.4000-519G>A	intron_variant	Intron 24 of 44	5		ENSP00000483259.1	A0A087X0B9
PTPRQ	ENST00000551624.1 link	n.262-519G>A	intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.0205

AC:

3115

AN:

152010

Hom.:

104

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00976

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.0153

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

GnomAD4 genome

AF:

0.0205

AC:

3121

AN:

152128

Hom.:

104

Cov.:

AF XY:

0.0199

AC XY:

1480

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.0699

AC:

2901

AN:

41486

American (AMR)

AF:

0.00975

AC:

149

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.000415

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10574

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000456

AC:

AN:

68002

Other (OTH)

AF:

0.0152

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

140

279

419

558

698

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<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:

0.0162

Hom.:

Bravo

AF:

0.0235

Asia WGS

AF:

0.00577

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.98

(source)

DANN

Benign

0.62

PhyloP100

0.36

Mutation Taster

=100/0

polymorphism

(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