Genetic Variant PTPRQ:c.6603-97A>G (chr12-80673072-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001145026.2(PTPRQ):c.6603-97A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 1,450,004 control chromosomes in the GnomAD database, including 92,823 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 13742 hom., cov: 32)

Exomes 𝑓: 0.34 ( 79081 hom. )

Consequence

PTPRQ
NM_001145026.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.31

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:

LOC105369867 (HGNC:):

LOC105369867 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 12-80673072-A-G is Benign according to our data. Variant chr12-80673072-A-G is described in ClinVar as [Benign]. Clinvar id is 1271771.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRQ	NM_001145026.2 link	c.6603-97A>G		intron_variant	Intron 42 of 44	ENST00000644991.3	NP_001138498.1	A0A087WZU1
LOC105369867	XR_007063388.1 link	n.130+34037T>C		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRQ	ENST00000644991.3 link	c.6603-97A>G		intron_variant	Intron 42 of 44		NM_001145026.2	ENSP00000495607.1		A0A087WZU1
PTPRQ	ENST00000616559.4 link	c.6702-97A>G		intron_variant	Intron 42 of 44	5		ENSP00000483259.1		A0A087X0B9

Frequencies

GnomAD3 genomes

AF:

0.406

AC:

61628

AN:

151866

Hom.:

13716

Cov.:

show subpopulations

Gnomad AFR

AF:

0.604

Gnomad AMI

AF:

0.163

Gnomad AMR

AF:

0.336

Gnomad ASJ

AF:

0.335

Gnomad EAS

AF:

0.248

Gnomad SAS

AF:

0.267

Gnomad FIN

AF:

0.342

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.341

Gnomad OTH

AF:

0.361

GnomAD4 exome

AF:

0.345

AC:

447472

AN:

1298020

Hom.:

79081

AF XY:

0.342

AC XY:

216816

AN XY:

634658

show subpopulations

Gnomad4 AFR exome

AF:

0.620

Gnomad4 AMR exome

AF:

0.305

Gnomad4 ASJ exome

AF:

0.340

Gnomad4 EAS exome

AF:

0.268

Gnomad4 SAS exome

AF:

0.272

Gnomad4 FIN exome

AF:

0.351

Gnomad4 NFE exome

AF:

0.345

Gnomad4 OTH exome

AF:

0.344

GnomAD4 genome

AF:

0.406

AC:

61699

AN:

151984

Hom.:

13742

Cov.:

AF XY:

0.402

AC XY:

29835

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.604

Gnomad4 AMR

AF:

0.336

Gnomad4 ASJ

AF:

0.335

Gnomad4 EAS

AF:

0.247

Gnomad4 SAS

AF:

0.266

Gnomad4 FIN

AF:

0.342

Gnomad4 NFE

AF:

0.341

Gnomad4 OTH

AF:

0.361

Alfa

AF:

0.334

Hom.:

8341

Bravo

AF:

0.413

Asia WGS

AF:

0.255

AC:

886

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.12

DANN

Benign

0.77

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

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