Genetic Variant PTPRQ:c.19+1283T>C (chr12-80436384-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 4P and 10B. PVS1_StrongBP6_ModerateBS1BS2

The ENST00000547376.5(PTPRQ):c.757+2T>C variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00472 in 370,210 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0050 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0045 ( 3 hom. )

Consequence

PTPRQ
ENST00000547376.5 splice_donor, intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.99

Variant links:

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]

PTPRQ links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.24316682 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.

BP6

Variant 12-80436384-T-C is Benign according to our data. Variant chr12-80436384-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2570840.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00504 (767/152268) while in subpopulation NFE AF= 0.00835 (568/68030). AF 95% confidence interval is 0.00778. There are 2 homozygotes in gnomad4. There are 368 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
PTPRQ	ENST00000616559.4 link	c.19+1283T>C	intron_variant	Intron 1 of 44	5	ENSP00000483259.1	A0A087X0B9
PTPRQ	ENST00000547376.5 link	c.757+2T>C	splice_donor_variant, intron_variant	Intron 9 of 11	5	ENSP00000448844.1	F8VXI2
PTPRQ	ENST00000551042.5 link	c.499+1283T>C	intron_variant	Intron 11 of 13	5	ENSP00000447522.1	F8W122
PTPRQ	ENST00000551573.5 link	c.547+1283T>C	intron_variant	Intron 6 of 8	3	ENSP00000449133.1	F8VW52

Frequencies

GnomAD3 genomes

AF:

0.00504

AC:

767

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00193

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00414

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00835

Gnomad OTH

AF:

0.00575

GnomAD3 exomes

AF:

0.00435

AC:

376

AN:

86394

Hom.:

AF XY:

0.00447

AC XY:

214

AN XY:

47834

show subpopulations

Gnomad AFR exome

AF:

0.00113

Gnomad AMR exome

AF:

0.00325

Gnomad ASJ exome

AF:

0.00148

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000415

Gnomad FIN exome

AF:

0.00429

Gnomad NFE exome

AF:

0.00837

Gnomad OTH exome

AF:

0.00517

GnomAD4 exome

AF:

0.00449

AC:

979

AN:

217942

Hom.:

Cov.:

AF XY:

0.00430

AC XY:

534

AN XY:

124296

show subpopulations

Gnomad4 AFR exome

AF:

0.00113

Gnomad4 AMR exome

AF:

0.00292

Gnomad4 ASJ exome

AF:

0.00211

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000258

Gnomad4 FIN exome

AF:

0.00449

Gnomad4 NFE exome

AF:

0.00689

Gnomad4 OTH exome

AF:

0.00580

GnomAD4 genome

AF:

0.00504

AC:

767

AN:

152268

Hom.:

Cov.:

AF XY:

0.00494

AC XY:

368

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00193

Gnomad4 AMR

AF:

0.00288

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00414

Gnomad4 NFE

AF:

0.00835

Gnomad4 OTH

AF:

0.00569

Alfa

AF:

0.00277

Hom.:

Bravo

AF:

0.00508

TwinsUK

AF:

0.00755

AC:

ALSPAC

AF:

0.00804

AC:

ExAC

AF:

0.00157

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PTPRQ: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Benign

0.89

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.84

GERP RS

3.7

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over