rs10506828

Variant names:

• chr12-80516926-A-T
• rs10506828
• NM_001145026.2:c.2678+6483A>T

Variant summary

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

The NM_001145026.2(PTPRQ):​c.2678+6483A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 152,008 control chromosomes in the GnomAD database, including 23,320 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 0.50 (23320 hom., cov: 31)
• Consequence: PTPRQ NM_001145026.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243
• Publications: 1 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
• hearing loss, autosomal recessive

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

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRQ	NM_001145026.2	c.2678+6483A>T		intron_variant	Intron 17 of 44	ENST00000644991.3	NP_001138498.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRQ	ENST00000644991.3	c.2678+6483A>T		intron_variant	Intron 17 of 44		NM_001145026.2	ENSP00000495607.1
PTPRQ	ENST00000616559.4	c.2804+6483A>T		intron_variant	Intron 18 of 44	5		ENSP00000483259.1
PTPRQ	ENST00000547485.1	n.156+4129A>T		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76652 AN: 151890 Hom.: 23312 Cov.: 31

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.537

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

GnomAD4 genome AF: 0.504 AC: 76667 AN: 152008 Hom.: 23320 Cov.: 31 AF XY: 0.510 AC XY: 37859 AN XY: 74288

African (AFR) AF: 0.155 AC: 6413 AN: 41474

American (AMR) AF: 0.538 AC: 8214 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 2030 AN: 3472

East Asian (EAS) AF: 0.394 AC: 2030 AN: 5152

South Asian (SAS) AF: 0.668 AC: 3217 AN: 4818

European-Finnish (FIN) AF: 0.706 AC: 7461 AN: 10566

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.671 AC: 45594 AN: 67940

Other (OTH) AF: 0.537 AC: 1129 AN: 2104

Alfa AF: 0.583 Hom.: 3519

Bravo AF: 0.471

Asia WGS AF: 0.541 AC: 1880 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.2
DANN	Benign	0.40
PhyloP100		0.24
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: rs10506828; hg19: chr12-80910705;