chr12-80444787-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001145026.2(PTPRQ):ā€‹c.101T>Gā€‹(p.Ile34Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000195 in 1,540,150 control chromosomes in the GnomAD database, with no homozygous occurrence. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

PTPRQ
NM_001145026.2 missense

Scores

5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.42
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PTPRQNM_001145026.2 linkuse as main transcriptc.101T>G p.Ile34Ser missense_variant 2/45 ENST00000644991.3 NP_001138498.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PTPRQENST00000644991.3 linkuse as main transcriptc.101T>G p.Ile34Ser missense_variant 2/45 NM_001145026.2 ENSP00000495607 P2

Frequencies

GnomAD3 genomes
AF:
0.00000659
AC:
1
AN:
151844
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000144
AC:
2
AN:
1388306
Hom.:
0
Cov.:
30
AF XY:
0.00000146
AC XY:
1
AN XY:
684926
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.33e-7
Gnomad4 OTH exome
AF:
0.0000175
GnomAD4 genome
AF:
0.00000659
AC:
1
AN:
151844
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74176
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGeneDxJul 12, 2022Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.36
BayesDel_addAF
Uncertain
0.065
T
BayesDel_noAF
Benign
-0.14
CADD
Benign
15
DANN
Benign
0.97
DEOGEN2
Benign
0.10
T;T;T;T;.;.
Eigen
Benign
-0.47
Eigen_PC
Benign
-0.46
FATHMM_MKL
Benign
0.76
D
LIST_S2
Benign
0.57
T;T;T;T;.;T
M_CAP
Benign
0.073
D
MetaRNN
Uncertain
0.45
T;T;T;T;T;T
MetaSVM
Benign
-0.89
T
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.41
T
PROVEAN
Uncertain
-3.7
D;D;D;.;.;.
REVEL
Benign
0.27
Sift
Benign
0.21
T;T;T;.;.;.
Sift4G
Uncertain
0.0040
D;D;D;D;D;.
Vest4
0.25, 0.34
MutPred
0.65
.;.;.;Gain of catalytic residue at S78 (P = 5e-04);.;.;
MVP
0.23
ClinPred
0.18
T
GERP RS
2.0
gMVP
0.69

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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.

Other links and lift over

dbSNP: rs1009535082; hg19: chr12-80838567; API