12-80444232-T-C

Position:

• chr12-80444232-T-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The ENST00000616559.4(PTPRQ):​c.180+320T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.964 in 615,774 control chromosomes in the GnomAD database, including 287,007 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.97 (71192 hom., cov: 25)
  • Exomes 𝑓: 0.96 (215815 hom.)
• Consequence: PTPRQ ENST00000616559.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.80

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 Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 12-80444232-T-C is Benign according to our data. Variant chr12-80444232-T-C is described in ClinVar as [Benign]. Clinvar id is 1296901.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.988 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRQ	NM_001145026.2			upstream_gene_variant		ENST00000644991.3	NP_001138498.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRQ	ENST00000644991.3			upstream_gene_variant			NM_001145026.2	ENSP00000495607	P2

Frequencies

GnomAD3 genomes AF: 0.971 AC: 146193 AN: 150528 Hom.: 71138 Cov.: 25

Gnomad AFR AF: 0.996

Gnomad AMI AF: 0.962

Gnomad AMR AF: 0.940

Gnomad ASJ AF: 0.996

Gnomad EAS AF: 0.802

Gnomad SAS AF: 0.967

Gnomad FIN AF: 0.897

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.986

Gnomad OTH AF: 0.970

GnomAD4 exome AF: 0.961 AC: 447214 AN: 465128 Hom.: 215815 Cov.: 5 AF XY: 0.963 AC XY: 244233 AN XY: 253562

Gnomad4 AFR exome AF: 0.998

Gnomad4 AMR exome AF: 0.894

Gnomad4 ASJ exome AF: 0.996

Gnomad4 EAS exome AF: 0.766

Gnomad4 SAS exome AF: 0.970

Gnomad4 FIN exome AF: 0.906

Gnomad4 NFE exome AF: 0.987

Gnomad4 OTH exome AF: 0.967

GnomAD4 genome AF: 0.971 AC: 146304 AN: 150646 Hom.: 71192 Cov.: 25 AF XY: 0.966 AC XY: 71013 AN XY: 73532

Gnomad4 AFR AF: 0.996

Gnomad4 AMR AF: 0.940

Gnomad4 ASJ AF: 0.996

Gnomad4 EAS AF: 0.803

Gnomad4 SAS AF: 0.967

Gnomad4 FIN AF: 0.897

Gnomad4 NFE AF: 0.986

Gnomad4 OTH AF: 0.967

Alfa AF: 0.973 Hom.: 16489

Bravo AF: 0.972

Asia WGS AF: 0.894 AC: 3109 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Benign	0.85

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10746166; hg19: chr12-80838012;