rs200166814

Positions:

chr12-80670476-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001145026.2(PTPRQ):c.6586A>G(p.Met2196Val) variant causes a missense change. The variant allele was found at a frequency of 0.00202 in 1,549,064 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 5 hom. )

Consequence

PTPRQ
NM_001145026.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 6.85

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 links:

LOC105369867 (HGNC:):

LOC105369867 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02842471).

BP6

Variant 12-80670476-A-G is Benign according to our data. Variant chr12-80670476-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 423816.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=1}.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00135 (205/152170) while in subpopulation NFE AF= 0.00249 (169/67976). AF 95% confidence interval is 0.00218. There are 0 homozygotes in gnomad4. There are 92 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 5 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRQ	NM_001145026.2 linkuse as main transcript	c.6586A>G	p.Met2196Val	missense_variant	42/45	ENST00000644991.3
LOC105369867	XR_007063388.1 linkuse as main transcript	n.130+36633T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRQ	ENST00000644991.3 linkuse as main transcript	c.6586A>G	p.Met2196Val	missense_variant	42/45		NM_001145026.2	P2
PTPRQ	ENST00000616559.4 linkuse as main transcript	c.6685A>G	p.Met2229Val	missense_variant	42/45	5		A2

Frequencies

GnomAD3 genomes

AF:

0.00135

AC:

205

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00249

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00137

AC:

213

AN:

155238

Hom.:

AF XY:

0.00116

AC XY:

AN XY:

81886

show subpopulations

Gnomad AFR exome

AF:

0.000248

Gnomad AMR exome

AF:

0.00177

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000449

Gnomad FIN exome

AF:

0.000296

Gnomad NFE exome

AF:

0.00219

Gnomad OTH exome

AF:

0.00481

GnomAD4 exome

AF:

0.00209

AC:

2917

AN:

1396894

Hom.:

Cov.:

AF XY:

0.00202

AC XY:

1392

AN XY:

688826

show subpopulations

Gnomad4 AFR exome

AF:

0.000350

Gnomad4 AMR exome

AF:

0.00184

Gnomad4 ASJ exome

AF:

0.0000398

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000585

Gnomad4 FIN exome

AF:

0.000708

Gnomad4 NFE exome

AF:

0.00248

Gnomad4 OTH exome

AF:

0.00152

GnomAD4 genome

AF:

0.00135

AC:

205

AN:

152170

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00249

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00212

Hom.:

Bravo

AF:

0.00141

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.00189

AC:

ExAC

AF:

0.00102

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Autosomal recessive nonsyndromic hearing loss 84A;C4540024:Hearing loss, autosomal dominant 73

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Oct 31, 2018

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Mar 06, 2017

The M2196V variant in the PTPRQ gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The M2196V variant is observed in 19/9348 (0.2%) alleles from individuals of European background, in the ExAC dataset (Lek et al., 2016). The M2196V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Methionine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret M2196V as a variant of uncertain significance. -

PTPRQ-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 05, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0024

T;.;.

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.84

T;.;T

M_CAP

Benign

0.0034

MetaRNN

Benign

0.028

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.49

Sift4G

Benign

0.16

T;T;.

Vest4

0.56

MVP

0.17

ClinPred

0.019

GERP RS

5.7

gMVP

0.25

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over