rs1565706749

Variant names:

• chr12-80444133-T-TA
• rs1565706749
• ENST00000616559.4:c.180+221_180+222insA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000551573.5(PTPRQ):​c.708+221_708+222insA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00218 in 278,800 control chromosomes in the GnomAD database, including 7 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0036 (5 hom., cov: 28)
  • Exomes 𝑓: 0.00068 (2 hom.)
• Consequence: PTPRQ ENST00000551573.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.66
• Publications: 0 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, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
• hearing loss, autosomal recessive

  Inheritance: Unknown, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• hearing loss, autosomal dominant 73

  Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 12-80444133-T-TA is Benign according to our data. Variant chr12-80444133-T-TA is described in ClinVar as Likely_benign. ClinVar VariationId is 1212235.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00364 (514/141110) while in subpopulation AFR AF = 0.0126 (502/39948). AF 95% confidence interval is 0.0117. There are 5 homozygotes in GnomAd4. There are 233 alleles in the male GnomAd4 subpopulation. Median coverage is 28. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AR,SD,AD,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000551573.5. 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.-213_-212insA		upstream_gene	N/A	NP_001138498.1	A0A087WZU1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRQ	ENST00000616559.4	TSL:5	c.180+221_180+222insA		intron	N/A	ENSP00000483259.1	A0A087X0B9
	PTPRQ	ENST00000547376.5	TSL:5	c.918+221_918+222insA		intron	N/A	ENSP00000448844.1	F8VXI2
	PTPRQ	ENST00000551042.5	TSL:5	c.660+221_660+222insA		intron	N/A	ENSP00000447522.1	F8W122

Frequencies

GnomAD3 genomes AF: 0.00360 AC: 507 AN: 141002 Hom.: 5 Cov.: 28

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000695

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00104

GnomAD4 exome AF: 0.000683 AC: 94 AN: 137690 Hom.: 2 Cov.: 0 AF XY: 0.000565 AC XY: 42 AN XY: 74276

African (AFR) AF: 0.0302 AC: 71 AN: 2354

American (AMR) AF: 0.00180 AC: 8 AN: 4448

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3494

East Asian (EAS) AF: 0.00 AC: 0 AN: 7330

South Asian (SAS) AF: 0.0000916 AC: 2 AN: 21832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7872

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 520

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 82404

Other (OTH) AF: 0.00175 AC: 13 AN: 7436

GnomAD4 genome AF: 0.00364 AC: 514 AN: 141110 Hom.: 5 Cov.: 28 AF XY: 0.00338 AC XY: 233 AN XY: 68848

African (AFR) AF: 0.0126 AC: 502 AN: 39948

American (AMR) AF: 0.000694 AC: 10 AN: 14416

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3286

East Asian (EAS) AF: 0.00 AC: 0 AN: 5124

South Asian (SAS) AF: 0.00 AC: 0 AN: 4406

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9044

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 61754

Other (OTH) AF: 0.00103 AC: 2 AN: 1950

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7

Splicing

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

Other links and lift over

dbSNP: rs1565706749; hg19: chr12-80837913;