Genetic Variant NM_001145026.2:c.98C>A (chr12-80444784-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001145026.2(PTPRQ):c.98C>A(p.Thr33Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000216 in 1,388,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T33I) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

PTPRQ
NM_001145026.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.11

Publications

6 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
hearing loss, autosomal recessive
Inheritance: Unknown, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hearing loss, autosomal dominant 73
Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

PTPRQ links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3305856).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRQ	NM_001145026.2	MANE Select	c.98C>A	p.Thr33Asn	missense	Exon 2 of 45	NP_001138498.1	A0A087WZU1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTPRQ	ENST00000644991.3	MANE Select	c.98C>A	p.Thr33Asn	missense	Exon 2 of 45	ENSP00000495607.1	A0A087WZU1
PTPRQ	ENST00000616559.4	TSL:5	c.224C>A	p.Thr75Asn	missense	Exon 3 of 45	ENSP00000483259.1	A0A087X0B9
PTPRQ	ENST00000547376.5	TSL:5	c.962C>A	p.Thr321Asn	missense	Exon 11 of 12	ENSP00000448844.1	F8VXI2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000130

AC:

AN:

153410

AF XY:

0.0000123

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000118

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000169

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000216

AC:

AN:

1388200

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

684888

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31178

American (AMR)

AF:

0.00

AC:

AN:

35478

Ashkenazi Jewish (ASJ)

AF:

0.0000404

AC:

AN:

24736

East Asian (EAS)

AF:

0.00

AC:

AN:

35232

South Asian (SAS)

AF:

0.00

AC:

AN:

78704

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48804

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5580

European-Non Finnish (NFE)

AF:

0.00000187

AC:

AN:

1071210

Other (OTH)

AF:

0.00

AC:

AN:

57278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00000282

Hom.:

129

ExAC

AF:

0.0000462

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.093

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.023

Eigen

Uncertain

0.31

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.73

M_CAP

Benign

0.025

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.45

PhyloP100

4.1

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.9

REVEL

Uncertain

0.32

Sift

Uncertain

0.0050

Sift4G

Pathogenic

0.0

Vest4

0.52

MutPred

0.46

Gain of catalytic residue at S78 (P = 0)

MVP

0.26

ClinPred

0.54

GERP RS

4.9

gMVP

0.47

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over