rs281865414

Positions:

• chr12-80460707-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NM_001145026.2(PTPRQ):​c.715A>G​(p.Arg239Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000776 in 399,338 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 7/8 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000093 (0 hom.)
• Consequence: PTPRQ NM_001145026.2 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1 O:1
• Conservation: PhyloP100: 3.11

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 12-80460707-A-G is Pathogenic according to our data. Variant chr12-80460707-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 156332.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.26196003). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRQ	NM_001145026.2	c.715A>G	p.Arg239Gly	missense_variant	6/45	ENST00000644991.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRQ	ENST00000644991.3	c.715A>G	p.Arg239Gly	missense_variant	6/45		NM_001145026.2	P2
PTPRQ	ENST00000616559.4	c.841A>G	p.Arg281Gly	missense_variant	7/45	5		A2

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152184 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.0000931 AC: 23 AN: 247154 Hom.: 0 Cov.: 0 AF XY: 0.000104 AC XY: 13 AN XY: 125234

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00121

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000695

Gnomad4 OTH exome AF: 0.000182

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152184 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74360

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000328

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.000478

Alfa AF: 0.0000693 Hom.: 0

Bravo AF: 0.0000945

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Autosomal recessive nonsyndromic hearing loss 84A Pathogenic:1 Other:1

Pathogenic, no assertion criteria provided	literature only	OMIM	Apr 09, 2010	- -
not provided, no classification provided	literature only	ClinVar Staff, National Center for Biotechnology Information (NCBI)	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_noAF	Benign	-0.79
CADD	Benign	15
DANN	Benign	0.71
DEOGEN2	Benign	0.012	T;.;.
LIST_S2	Benign	0.68	T;.;T
MetaRNN	Benign	0.26	T;T;T
Sift4G	Uncertain	0.0090	D;D;.
Vest4		0.20
gMVP		0.35

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

Publications

LitVar

Other links and lift over

dbSNP: rs281865414; hg19: chr12-80849470;