rs7963963

Variant names:

• chr12-80613748-T-C
• rs7963963
• NM_001145026.2:c.5075T>C

Variant summary

Our verdict is Benign. The variant received -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 (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. 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:3
• Conservation: PhyloP100: 4.55
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 84A

  Inheritance: AR, SD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• hearing loss, autosomal recessive

  Inheritance: Unknown, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hearing loss, autosomal dominant 73

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000304204 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 586389.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145026.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRQ	NM_001145026.2	MANE Select	c.5075T>C	p.Ile1692Thr	missense	Exon 29 of 45	NP_001138498.1	A0A087WZU1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRQ	ENST00000644991.3	MANE Select	c.5075T>C	p.Ile1692Thr	missense	Exon 29 of 45	ENSP00000495607.1	A0A087WZU1
	PTPRQ	ENST00000616559.4	TSL:5	c.5201T>C	p.Ile1734Thr	missense	Exon 30 of 45	ENSP00000483259.1	A0A087X0B9
	ENSG00000304204	ENST00000801015.1		n.101-33339A>G		intron	N/A

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

GnomAD2 exomes AF: 0.0296 AC: 4510 AN: 152480 AF XY: 0.0265

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 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

African (AFR) AF: 0.231 AC: 7207 AN: 31248

American (AMR) AF: 0.0212 AC: 755 AN: 35642

Ashkenazi Jewish (ASJ) AF: 0.0333 AC: 832 AN: 24984

East Asian (EAS) AF: 0.00 AC: 0 AN: 35590

South Asian (SAS) AF: 0.0139 AC: 1101 AN: 78998

European-Finnish (FIN) AF: 0.0194 AC: 954 AN: 49254

Middle Eastern (MID) AF: 0.0186 AC: 105 AN: 5656

European-Non Finnish (NFE) AF: 0.0213 AC: 22950 AN: 1076050

Other (OTH) AF: 0.0328 AC: 1891 AN: 57706

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

African (AFR) AF: 0.228 AC: 9385 AN: 41220

American (AMR) AF: 0.0333 AC: 501 AN: 15030

Ashkenazi Jewish (ASJ) AF: 0.0345 AC: 118 AN: 3424

East Asian (EAS) AF: 0.000196 AC: 1 AN: 5112

South Asian (SAS) AF: 0.0123 AC: 59 AN: 4780

European-Finnish (FIN) AF: 0.0184 AC: 195 AN: 10612

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0230 AC: 1537 AN: 66966

Other (OTH) AF: 0.0566 AC: 118 AN: 2086

Alfa AF: 0.0376 Hom.: 1491

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

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
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.1	T
PhyloP100		4.5
PrimateAI	Uncertain	0.56	T
Sift4G	Uncertain	0.0040	D
Vest4		0.28
ClinPred		0.024	T
GERP RS		6.0
gMVP		0.15
Mutation Taster		=92/8	polymorphism (auto)

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

Other links and lift over

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