12-80646484-AG-AGG

Variant names:

• chr12-80646484-A-AG
• rs11465200
• NM_001145026.2:c.5916-2409dupG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001145026.2(PTPRQ):​c.5916-2409dupG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,086 control chromosomes in the GnomAD database, including 3,209 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (3209 hom., cov: 29)
• Consequence: PTPRQ NM_001145026.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.546
• 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: 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

ENSG00000304204 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRQ	NM_001145026.2	c.5916-2409dupG		intron_variant	Intron 35 of 44	ENST00000644991.3	NP_001138498.1
LOC105369867	XR_007063388.1	n.130+60624dupC		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRQ	ENST00000644991.3	c.5916-2413_5916-2412insG		intron_variant	Intron 35 of 44		NM_001145026.2	ENSP00000495607.1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26539 AN: 151968 Hom.: 3205 Cov.: 29

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0521

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.175 AC: 26574 AN: 152086 Hom.: 3209 Cov.: 29 AF XY: 0.173 AC XY: 12898 AN XY: 74374

African (AFR) AF: 0.329 AC: 13654 AN: 41444

American (AMR) AF: 0.195 AC: 2972 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 353 AN: 3472

East Asian (EAS) AF: 0.212 AC: 1095 AN: 5162

South Asian (SAS) AF: 0.124 AC: 596 AN: 4824

European-Finnish (FIN) AF: 0.0521 AC: 553 AN: 10616

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6936 AN: 67980

Other (OTH) AF: 0.157 AC: 332 AN: 2116

Alfa AF: 0.142 Hom.: 272

Bravo AF: 0.190

Asia WGS AF: 0.165 AC: 572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.55
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: rs11465200; hg19: chr12-81040263;