12-80673072-A-G

Variant names:

• chr12-80673072-A-G
• rs950124
• NM_001145026.2:c.6603-97A>G

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.6603-97A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 1,450,004 control chromosomes in the GnomAD database, including 92,823 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (13742 hom., cov: 32)
  • Exomes 𝑓: 0.34 (79081 hom.)
• Consequence: PTPRQ NM_001145026.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.31
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 12-80673072-A-G is Benign according to our data. Variant chr12-80673072-A-G is described in ClinVar as Benign. ClinVar VariationId is 1271771.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRQ	NM_001145026.2	c.6603-97A>G		intron_variant	Intron 42 of 44	ENST00000644991.3	NP_001138498.1
LOC105369867	XR_007063388.1	n.130+34037T>C		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRQ	ENST00000644991.3	c.6603-97A>G		intron_variant	Intron 42 of 44		NM_001145026.2	ENSP00000495607.1
PTPRQ	ENST00000616559.4	c.6702-97A>G		intron_variant	Intron 42 of 44	5		ENSP00000483259.1
ENSG00000304204	ENST00000801015.1	n.100+34037T>C		intron_variant	Intron 1 of 2
ENSG00000304204	ENST00000801016.1	n.101-20721T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61628 AN: 151866 Hom.: 13716 Cov.: 32

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.361

GnomAD4 exome AF: 0.345 AC: 447472 AN: 1298020 Hom.: 79081 AF XY: 0.342 AC XY: 216816 AN XY: 634658

African (AFR) AF: 0.620 AC: 17021 AN: 27434

American (AMR) AF: 0.305 AC: 6695 AN: 21984

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 7249 AN: 21346

East Asian (EAS) AF: 0.268 AC: 8874 AN: 33072

South Asian (SAS) AF: 0.272 AC: 17265 AN: 63574

European-Finnish (FIN) AF: 0.351 AC: 15847 AN: 45190

Middle Eastern (MID) AF: 0.333 AC: 1221 AN: 3664

European-Non Finnish (NFE) AF: 0.345 AC: 354988 AN: 1028500

Other (OTH) AF: 0.344 AC: 18312 AN: 53256

GnomAD4 genome AF: 0.406 AC: 61699 AN: 151984 Hom.: 13742 Cov.: 32 AF XY: 0.402 AC XY: 29835 AN XY: 74292

African (AFR) AF: 0.604 AC: 25038 AN: 41428

American (AMR) AF: 0.336 AC: 5125 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1162 AN: 3466

East Asian (EAS) AF: 0.247 AC: 1274 AN: 5154

South Asian (SAS) AF: 0.266 AC: 1285 AN: 4822

European-Finnish (FIN) AF: 0.342 AC: 3621 AN: 10578

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23195 AN: 67946

Other (OTH) AF: 0.361 AC: 763 AN: 2116

Alfa AF: 0.348 Hom.: 12189

Bravo AF: 0.413

Asia WGS AF: 0.255 AC: 886 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

- -

Jul 23, 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	-0.91
CADD	Benign	0.12
DANN	Benign	0.77
PhyloP100		-2.3
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: rs950124; hg19: chr12-81066851; COSMIC: COSV57038982;