12-80444137-T-A

Position:

• chr12-80444137-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000616559.4(PTPRQ):​c.180+225T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00218 in 282,328 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0036 (5 hom., cov: 28)
  • Exomes 𝑓: 0.00073 (2 hom.)
• Consequence: PTPRQ ENST00000616559.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.239

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 12-80444137-T-A is Benign according to our data. Variant chr12-80444137-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 1208782.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00362 (513/141678) while in subpopulation AFR AF= 0.0125 (502/40072). AF 95% confidence interval is 0.0116. There are 5 homozygotes in gnomad4. There are 233 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 SD gene

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+225T>A		intron_variant		5		ENSP00000448844
PTPRQ	ENST00000551042.5	c.660+225T>A		intron_variant		5		ENSP00000447522
PTPRQ	ENST00000551573.5	c.708+225T>A		intron_variant		3		ENSP00000449133
PTPRQ	ENST00000616559.4	c.180+225T>A		intron_variant		5		ENSP00000483259	A2

Frequencies

GnomAD3 genomes AF: 0.00357 AC: 506 AN: 141564 Hom.: 5 Cov.: 28

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000623

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: 0.00

Gnomad OTH AF: 0.00103

GnomAD4 exome AF: 0.000732 AC: 103 AN: 140650 Hom.: 2 Cov.: 0 AF XY: 0.000592 AC XY: 45 AN XY: 75950

Gnomad4 AFR exome AF: 0.0330

Gnomad4 AMR exome AF: 0.00175

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000899

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00171

GnomAD4 genome AF: 0.00362 AC: 513 AN: 141678 Hom.: 5 Cov.: 28 AF XY: 0.00337 AC XY: 233 AN XY: 69162

Gnomad4 AFR AF: 0.0125

Gnomad4 AMR AF: 0.000622

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00102

Alfa AF: 0.00287 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 13, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.3
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1438074322; hg19: chr12-80837917;