12-80444099-G-C

Position:

• chr12-80444099-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000616559.4(PTPRQ):​c.180+187G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0174 in 393,974 control chromosomes in the GnomAD database, including 501 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.044 (475 hom., cov: 31)
  • Exomes 𝑓: 0.0018 (26 hom.)
• Consequence: PTPRQ ENST00000616559.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.92

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=-0.82).
• BP6: Variant 12-80444099-G-C is Benign according to our data. Variant chr12-80444099-G-C is described in ClinVar as [Benign]. Clinvar id is 1227302.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRQ	ENST00000547376.5	c.918+187G>C		intron_variant		5		ENSP00000448844
PTPRQ	ENST00000551042.5	c.660+187G>C		intron_variant		5		ENSP00000447522
PTPRQ	ENST00000551573.5	c.708+187G>C		intron_variant		3		ENSP00000449133
PTPRQ	ENST00000616559.4	c.180+187G>C		intron_variant		5		ENSP00000483259	A2

Frequencies

GnomAD3 genomes AF: 0.0435 AC: 6373 AN: 146556 Hom.: 470 Cov.: 31

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0138

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000431

Gnomad FIN AF: 0.000110

Gnomad MID AF: 0.0135

Gnomad NFE AF: 0.000553

Gnomad OTH AF: 0.0328

GnomAD4 exome AF: 0.00177 AC: 437 AN: 247368 Hom.: 26 Cov.: 0 AF XY: 0.00147 AC XY: 192 AN XY: 130920

Gnomad4 AFR exome AF: 0.0685

Gnomad4 AMR exome AF: 0.00421

Gnomad4 ASJ exome AF: 0.000127

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000239

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000129

Gnomad4 OTH exome AF: 0.00410

GnomAD4 genome AF: 0.0437 AC: 6403 AN: 146606 Hom.: 475 Cov.: 31 AF XY: 0.0426 AC XY: 3026 AN XY: 71040

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.0138

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000217

Gnomad4 FIN AF: 0.000110

Gnomad4 NFE AF: 0.000553

Gnomad4 OTH AF: 0.0326

Alfa AF: 0.00199 Hom.: 1

Bravo AF: 0.0505

Asia WGS AF: 0.00808 AC: 28 AN: 3478

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	Dec 22, 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	-0.82
CADD	Benign	9.9
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs58265080; hg19: chr12-80837879;