Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001145026.2(PTPRQ):c.386T>G(p.Ile129Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

PTPRQ
NM_001145026.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.68

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive nonsyndromic hearing loss 84A
Inheritance: AR, SD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
hearing loss, autosomal recessive
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
hearing loss, autosomal dominant 73
Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PTPRQ links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145026.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRQ	NM_001145026.2	MANE Select	c.386T>G	p.Ile129Ser	missense	Exon 3 of 45	NP_001138498.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PTPRQ	ENST00000644991.3	MANE Select	c.386T>G	p.Ile129Ser	missense	Exon 3 of 45	ENSP00000495607.1
PTPRQ	ENST00000616559.4	TSL:5	c.512T>G	p.Ile171Ser	missense	Exon 4 of 45	ENSP00000483259.1
PTPRQ	ENST00000551042.5	TSL:5	c.992T>G	p.Ile331Ser	missense	Exon 14 of 14	ENSP00000447522.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hearing loss, autosomal dominant 73 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.21

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.84

M_CAP

Uncertain

0.10

MetaRNN

Pathogenic

0.79

MetaSVM

Uncertain

-0.031

PhyloP100

5.7

PrimateAI

Uncertain

0.74

PROVEAN

Pathogenic

-4.4

REVEL

Uncertain

0.52

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.88

MutPred

0.64

Gain of catalytic residue at Y169 (P = 0.0014)

MVP

0.37

ClinPred

1.0

GERP RS

5.8

gMVP

0.81

Mutation Taster

=68/32

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.75

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.75

Position offset: -1

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

Publications

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NM_001145026.2:c.386T>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over