12-80425096-A-G

Variant names:

• chr12-80425096-A-G
• rs10746164
• ENST00000547376.5:c.205A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000551573.5(PTPRQ):​c.253A>G​(p.Arg85Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 454,882 control chromosomes in the GnomAD database, including 141,756 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.72 (41371 hom., cov: 32)
  • Exomes 𝑓: 0.81 (100385 hom.)
• Consequence: PTPRQ ENST00000551573.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:3
• Conservation: PhyloP100: 2.68

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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.0327069E-6).
• BP6: Variant 12-80425096-A-G is Benign according to our data. Variant chr12-80425096-A-G is described in ClinVar as [Benign]. Clinvar id is 1174628.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-80425096-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRQ	ENST00000547376.5	c.205A>G	p.Arg69Gly	missense_variant	Exon 6 of 12	5		ENSP00000448844.1
PTPRQ	ENST00000551042.5	c.205A>G	p.Arg69Gly	missense_variant	Exon 9 of 14	5		ENSP00000447522.1
PTPRQ	ENST00000551573.5	c.253A>G	p.Arg85Gly	missense_variant	Exon 4 of 9	3		ENSP00000449133.1

Frequencies

GnomAD3 genomes AF: 0.717 AC: 108876 AN: 151902 Hom.: 41373 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.790

Gnomad AMR AF: 0.695

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.771

Gnomad SAS AF: 0.824

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.854

Gnomad OTH AF: 0.762

GnomAD2 exomes AF: 0.773 AC: 98246 AN: 127130 AF XY: 0.788

Gnomad AFR exome AF: 0.419

Gnomad AMR exome AF: 0.626

Gnomad ASJ exome AF: 0.848

Gnomad EAS exome AF: 0.760

Gnomad FIN exome AF: 0.792

Gnomad NFE exome AF: 0.852

Gnomad OTH exome AF: 0.801

GnomAD4 exome AF: 0.808 AC: 244731 AN: 302862 Hom.: 100385 Cov.: 0 AF XY: 0.816 AC XY: 140776 AN XY: 172480

Gnomad4 AFR exome AF: 0.432 AC: 3707 AN: 8572

Gnomad4 AMR exome AF: 0.627 AC: 17015 AN: 27156

Gnomad4 ASJ exome AF: 0.844 AC: 9055 AN: 10732

Gnomad4 EAS exome AF: 0.761 AC: 7001 AN: 9194

Gnomad4 SAS exome AF: 0.829 AC: 49313 AN: 59504

Gnomad4 FIN exome AF: 0.795 AC: 9804 AN: 12338

Gnomad4 NFE exome AF: 0.854 AC: 135349 AN: 158426

Gnomad4 Remaining exome AF: 0.801 AC: 11359 AN: 14176

GnomAD4 genome AF: 0.716 AC: 108899 AN: 152020 Hom.: 41371 Cov.: 32 AF XY: 0.714 AC XY: 53074 AN XY: 74282

Gnomad4 AFR AF: 0.446 AC: 0.445648 AN: 0.445648

Gnomad4 AMR AF: 0.695 AC: 0.695242 AN: 0.695242

Gnomad4 ASJ AF: 0.844 AC: 0.844489 AN: 0.844489

Gnomad4 EAS AF: 0.771 AC: 0.770761 AN: 0.770761

Gnomad4 SAS AF: 0.823 AC: 0.823102 AN: 0.823102

Gnomad4 FIN AF: 0.787 AC: 0.786905 AN: 0.786905

Gnomad4 NFE AF: 0.854 AC: 0.854173 AN: 0.854173

Gnomad4 OTH AF: 0.762 AC: 0.76186 AN: 0.76186

Alfa AF: 0.802 Hom.: 20375

Bravo AF: 0.693

TwinsUK AF: 0.846 AC: 3137

ALSPAC AF: 0.857 AC: 3303

ExAC AF: 0.798 AC: 9662

Asia WGS AF: 0.780 AC: 2708 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:2

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.055	T;T;T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.42	T;T;T
MetaRNN	Benign	0.0000010	T;T;T
MetaSVM	Benign	-1.1	T
PROVEAN	Benign	-1.7	N;D;N
REVEL	Benign	0.086
Sift	Benign	0.46	T;D;T
Sift4G	Pathogenic	0.0	D;D;D
ClinPred		0.015	T
GERP RS		4.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10746164; hg19: chr12-80818876;