12-80457419-G-A

Position:

• chr12-80457419-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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/exons	MANE	Protein	UniProt
PTPRQ	NM_001145026.2	c.391-156G>A		intron_variant		ENST00000644991.3	NP_001138498.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRQ	ENST00000644991.3	c.391-156G>A		intron_variant			NM_001145026.2	ENSP00000495607.1
PTPRQ	ENST00000616559.4	c.517-156G>A		intron_variant		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

Gnomad4 AFR AF: 0.614

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.0562

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.351

Alfa AF: 0.222 Hom.: 507

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.15
DANN	Benign	0.33

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: rs10862125; hg19: chr12-80852758;