rs61729303
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
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
NM_001145026.2 missense
Scores
7
5
5
Clinical Significance
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]
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ACMG classification
Classification made for transcript
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. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 17 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PTPRQ | NM_001145026.2 | c.202G>A | p.Gly68Arg | missense_variant | 3/45 | ENST00000644991.3 | NP_001138498.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PTPRQ | ENST00000644991.3 | c.202G>A | p.Gly68Arg | missense_variant | 3/45 | NM_001145026.2 | ENSP00000495607 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00318 AC: 482AN: 151640Hom.: 11 Cov.: 32
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GnomAD3 exomes AF: 0.00914 AC: 1384AN: 151376Hom.: 44 AF XY: 0.00659 AC XY: 530AN XY: 80396
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GnomAD4 exome AF: 0.00143 AC: 1993AN: 1395674Hom.: 56 Cov.: 30 AF XY: 0.00119 AC XY: 817AN XY: 688350
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GnomAD4 genome AF: 0.00331 AC: 502AN: 151758Hom.: 17 Cov.: 32 AF XY: 0.00348 AC XY: 258AN XY: 74188
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
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 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jun 29, 2016 | - - |
PTPRQ-related disorder Benign:1
Benign, no assertion criteria provided | 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). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.;D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;.;.
REVEL
Uncertain
Sift
Pathogenic
D;.;.;.
Sift4G
Pathogenic
D;D;D;.
Vest4
0.89, 0.90
MutPred
0.57
.;Gain of catalytic residue at A112 (P = 0.0306);.;.;
MVP
ClinPred
T
GERP RS
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at