rs61729303

chr12-80445529-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001145026.2(PTPRQ):c.202G>A(p.Gly68Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00161 in 1,547,432 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0033 (17 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (56 hom.)
• Consequence: PTPRQ NM_001145026.2 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 7.08

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0070736706).
• BP6: Variant 12-80445529-G-A is Benign according to our data. Variant chr12-80445529-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 218516.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00331 (502/151758) while in subpopulation AMR AF= 0.0276 (419/15172). AF 95% confidence interval is 0.0254. There are 17 homozygotes in gnomad4. There are 258 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 11 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRQ	NM_001145026.2	c.202G>A	p.Gly68Arg	missense_variant	3/45	ENST00000644991.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRQ	ENST00000644991.3	c.202G>A	p.Gly68Arg	missense_variant	3/45		NM_001145026.2	P2

Frequencies

GnomAD3 genomes AF: 0.00318 AC: 482 AN: 151640 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00160

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0263

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000885

Gnomad OTH AF: 0.00480

GnomAD3 exomes AF: 0.00914 AC: 1384 AN: 151376 Hom.: 44 AF XY: 0.00659 AC XY: 530 AN XY: 80396

Gnomad AFR exome AF: 0.00244

Gnomad AMR exome AF: 0.0541

Gnomad ASJ exome AF: 0.000119

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000443

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000852

Gnomad OTH exome AF: 0.00774

GnomAD4 exome AF: 0.00143 AC: 1993 AN: 1395674 Hom.: 56 Cov.: 30 AF XY: 0.00119 AC XY: 817 AN XY: 688350

Gnomad4 AFR exome AF: 0.00108

Gnomad4 AMR exome AF: 0.0503

Gnomad4 ASJ exome AF: 0.0000399

Gnomad4 EAS exome AF: 0.0000280

Gnomad4 SAS exome AF: 0.0000634

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000511

Gnomad4 OTH exome AF: 0.00178

GnomAD4 genome AF: 0.00331 AC: 502 AN: 151758 Hom.: 17 Cov.: 32 AF XY: 0.00348 AC XY: 258 AN XY: 74188

Gnomad4 AFR AF: 0.00159

Gnomad4 AMR AF: 0.0276

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000885

Gnomad4 OTH AF: 0.00475

Alfa AF: 0.000587 Hom.: 0

Bravo AF: 0.00615

ESP6500AA AF: 0.00289 AC: 4

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000883 AC: 19

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Likely benign, criteria provided, single submitter	clinical testing	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	May 05, 2015	- -

PTPRQ-related condition Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 11, 2019

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

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Jun 29, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Pathogenic	0.21
Cadd	Pathogenic	28
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.017	T;T;.;.
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D;D;.;D
MetaRNN	Benign	0.0071	T;T;T;T
MetaSVM	Benign	-0.64	T
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.0	D;.;.;.
REVEL	Uncertain	0.45
Sift	Pathogenic	0.0	D;.;.;.
Sift4G	Pathogenic	0.0	D;D;D;.
Vest4		0.89, 0.90
MutPred		0.57		.;Gain of catalytic residue at A112 (P = 0.0306);.;.;
MVP		0.32
ClinPred		0.034	T
GERP RS		5.8
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs61729303; hg19: chr12-80839309;