rs1528288

Variant names:

• chr12-80547286-G-A
• rs1528288
• NM_001145026.2:c.4015+589G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145026.2(PTPRQ):​c.4015+589G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.952 in 152,214 control chromosomes in the GnomAD database, including 69,277 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.95 (69277 hom., cov: 31)
• Consequence: PTPRQ NM_001145026.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312
• 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, 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

LOC105369867 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.981 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.4015+589G>A		intron	N/A	NP_001138498.1	A0A087WZU1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRQ	ENST00000644991.3	MANE Select	c.4015+589G>A		intron	N/A	ENSP00000495607.1	A0A087WZU1
	PTPRQ	ENST00000616559.4	TSL:5	c.4141+589G>A		intron	N/A	ENSP00000483259.1	A0A087X0B9
	PTPRQ	ENST00000551624.1	TSL:3	n.*163G>A		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.952 AC: 144862 AN: 152096 Hom.: 69221 Cov.: 31

Gnomad AFR AF: 0.927

Gnomad AMI AF: 0.962

Gnomad AMR AF: 0.922

Gnomad ASJ AF: 0.993

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.931

Gnomad FIN AF: 0.977

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.987

Gnomad OTH AF: 0.960

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.952 AC: 144978 AN: 152214 Hom.: 69277 Cov.: 31 AF XY: 0.951 AC XY: 70739 AN XY: 74404

African (AFR) AF: 0.927 AC: 38486 AN: 41532

American (AMR) AF: 0.922 AC: 14083 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.993 AC: 3443 AN: 3466

East Asian (EAS) AF: 0.727 AC: 3753 AN: 5160

South Asian (SAS) AF: 0.931 AC: 4491 AN: 4824

European-Finnish (FIN) AF: 0.977 AC: 10366 AN: 10610

Middle Eastern (MID) AF: 0.980 AC: 288 AN: 294

European-Non Finnish (NFE) AF: 0.987 AC: 67166 AN: 68028

Other (OTH) AF: 0.960 AC: 2025 AN: 2110

Alfa AF: 0.964 Hom.: 9156

Bravo AF: 0.945

Asia WGS AF: 0.843 AC: 2934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.45
DANN	Benign	0.21
PhyloP100		-0.31
Mutation Taster		=100/0	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: rs1528288; hg19: chr12-80941065;