NM_001145026.2:c.391-156G>A

Variant names:

• chr12-80457419-G-A
• rs10862125
• NM_001145026.2:c.391-156G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001145026.2(PTPRQ):​c.391-156G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 151,920 control chromosomes in the GnomAD database, including 13,173 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.39 (13173 hom., cov: 33)
• Consequence: PTPRQ NM_001145026.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.19
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 12-80457419-G-A is Benign according to our data. Variant chr12-80457419-G-A is described in ClinVar as Benign. ClinVar VariationId is 1243212.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRQ	NM_001145026.2	c.391-156G>A		intron_variant	Intron 3 of 44	ENST00000644991.3	NP_001138498.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRQ	ENST00000644991.3	c.391-156G>A		intron_variant	Intron 3 of 44		NM_001145026.2	ENSP00000495607.1
PTPRQ	ENST00000616559.4	c.517-156G>A		intron_variant	Intron 4 of 44	5		ENSP00000483259.1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59034 AN: 151802 Hom.: 13155 Cov.: 33

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.0565

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.389 AC: 59093 AN: 151920 Hom.: 13173 Cov.: 33 AF XY: 0.383 AC XY: 28408 AN XY: 74252

African (AFR) AF: 0.614 AC: 25442 AN: 41424

American (AMR) AF: 0.361 AC: 5512 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1035 AN: 3468

East Asian (EAS) AF: 0.0562 AC: 291 AN: 5178

South Asian (SAS) AF: 0.259 AC: 1250 AN: 4824

European-Finnish (FIN) AF: 0.285 AC: 3012 AN: 10560

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21439 AN: 67884

Other (OTH) AF: 0.351 AC: 740 AN: 2110

Alfa AF: 0.245 Hom.: 656

Bravo AF: 0.403

Asia WGS AF: 0.166 AC: 580 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 29, 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	-0.92
CADD	Benign	0.15
DANN	Benign	0.33
PhyloP100		-1.2

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: rs10862125; hg19: chr12-80852758;