rs7963963

chr12-80613748-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001145026.2(PTPRQ):c.5075T>C(p.Ile1692Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0309 in 1,545,564 control chromosomes in the GnomAD database, including 2,365 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. I1692I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.079 (1150 hom., cov: 32)
  • Exomes 𝑓: 0.026 (1215 hom.)
• Consequence: PTPRQ NM_001145026.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.55

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]

LOC105369867 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016589165).
• BP6: Variant 12-80613748-T-C is Benign according to our data. Variant chr12-80613748-T-C is described in ClinVar as [Benign]. Clinvar id is 586389.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-80613748-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRQ	NM_001145026.2	c.5075T>C	p.Ile1692Thr	missense_variant	29/45	ENST00000644991.3
LOC105369867	XR_007063388.1	n.131-33339A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRQ	ENST00000644991.3	c.5075T>C	p.Ile1692Thr	missense_variant	29/45		NM_001145026.2	P2
PTPRQ	ENST00000616559.4	c.5201T>C	p.Ile1734Thr	missense_variant	30/45	5		A2

Frequencies

GnomAD3 genomes AF: 0.0791 AC: 11886 AN: 150318 Hom.: 1144 Cov.: 32

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0334

Gnomad ASJ AF: 0.0345

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.0123

Gnomad FIN AF: 0.0184

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0229

Gnomad OTH AF: 0.0572

GnomAD3 exomes AF: 0.0296 AC: 4510 AN: 152480 Hom.: 231 AF XY: 0.0265 AC XY: 2148 AN XY: 80944

Gnomad AFR exome AF: 0.230

Gnomad AMR exome AF: 0.0183

Gnomad ASJ exome AF: 0.0326

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0138

Gnomad FIN exome AF: 0.0196

Gnomad NFE exome AF: 0.0223

Gnomad OTH exome AF: 0.0216

GnomAD4 exome AF: 0.0257 AC: 35795 AN: 1395128 Hom.: 1215 Cov.: 31 AF XY: 0.0249 AC XY: 17134 AN XY: 688104

Gnomad4 AFR exome AF: 0.231

Gnomad4 AMR exome AF: 0.0212

Gnomad4 ASJ exome AF: 0.0333

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0139

Gnomad4 FIN exome AF: 0.0194

Gnomad4 NFE exome AF: 0.0213

Gnomad4 OTH exome AF: 0.0328

GnomAD4 genome AF: 0.0792 AC: 11919 AN: 150436 Hom.: 1150 Cov.: 32 AF XY: 0.0767 AC XY: 5638 AN XY: 73506

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.0333

Gnomad4 ASJ AF: 0.0345

Gnomad4 EAS AF: 0.000196

Gnomad4 SAS AF: 0.0123

Gnomad4 FIN AF: 0.0184

Gnomad4 NFE AF: 0.0230

Gnomad4 OTH AF: 0.0566

Alfa AF: 0.0317 Hom.: 555

Bravo AF: 0.0864

TwinsUK AF: 0.0227 AC: 84

ALSPAC AF: 0.0234 AC: 90

ESP6500AA AF: 0.223 AC: 309

ESP6500EA AF: 0.0267 AC: 85

ExAC AF: 0.0391 AC: 851

Asia WGS AF: 0.0170 AC: 61 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 24, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 21, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.23
Cadd	Benign	22
Dann	Uncertain	0.99
DEOGEN2	Benign	0.018	T;.;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	D;.;D
MetaRNN	Benign	0.0017	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.0019	P
PrimateAI	Uncertain	0.56	T
Sift4G	Uncertain	0.0040	D;D;.
Vest4		0.28
ClinPred		0.024	T
GERP RS		6.0
gMVP		0.15

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

Other links and lift over

dbSNP: rs7963963; hg19: chr12-81007527; COSMIC: COSV57046911;