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: 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

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.

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.6454-185T>G		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.6454-185T>G		intron	N/A	ENSP00000495607.1	A0A087WZU1
	PTPRQ	ENST00000616559.4	TSL:5	c.6553-185T>G		intron	N/A	ENSP00000483259.1	A0A087X0B9
	ENSG00000304204	ENST00000801015.1		n.100+36950A>C		intron	N/A

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

ClinVar submissions

Significance: 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
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;