NM_001145026.2:c.6454-185T>G

Variant names:

• chr12-80670159-T-G
• rs10506831
• NM_001145026.2:c.6454-185T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001145026.2(PTPRQ):​c.6454-185T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,136 control chromosomes in the GnomAD database, including 2,839 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.17 (2839 hom., cov: 32)
• Consequence: PTPRQ NM_001145026.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.09
• 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

ENSG00000304204 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 12-80670159-T-G is Benign according to our data. Variant chr12-80670159-T-G is described in ClinVar as Benign. ClinVar VariationId is 1280250.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRQ	NM_001145026.2	c.6454-185T>G		intron_variant	Intron 41 of 44	ENST00000644991.3	NP_001138498.1
LOC105369867	XR_007063388.1	n.130+36950A>C		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRQ	ENST00000644991.3	c.6454-185T>G		intron_variant	Intron 41 of 44		NM_001145026.2	ENSP00000495607.1
PTPRQ	ENST00000616559.4	c.6553-185T>G		intron_variant	Intron 41 of 44	5		ENSP00000483259.1
ENSG00000304204	ENST00000801015.1	n.100+36950A>C		intron_variant	Intron 1 of 2
ENSG00000304204	ENST00000801016.1	n.101-17808A>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25382 AN: 152018 Hom.: 2839 Cov.: 32

Gnomad AFR AF: 0.0423

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.0334

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.167 AC: 25371 AN: 152136 Hom.: 2839 Cov.: 32 AF XY: 0.167 AC XY: 12432 AN XY: 74364

African (AFR) AF: 0.0422 AC: 1753 AN: 41556

American (AMR) AF: 0.114 AC: 1734 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 710 AN: 3472

East Asian (EAS) AF: 0.0331 AC: 171 AN: 5162

South Asian (SAS) AF: 0.203 AC: 981 AN: 4822

European-Finnish (FIN) AF: 0.292 AC: 3085 AN: 10582

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16423 AN: 67964

Other (OTH) AF: 0.160 AC: 337 AN: 2106

Alfa AF: 0.196 Hom.: 435

Bravo AF: 0.148

Asia WGS AF: 0.0960 AC: 336 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.42
DANN	Benign	0.71
PhyloP100		-1.1
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: rs10506831; hg19: chr12-81063938;