12-42460650-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_153026.3(PRICKLE1):c.1655G>A(p.Gly552Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
PRICKLE1
NM_153026.3 missense
NM_153026.3 missense
Scores
9
9
Clinical Significance
Conservation
PhyloP100: 1.71
Genes affected
PRICKLE1 (HGNC:17019): (prickle planar cell polarity protein 1) This gene encodes a nuclear receptor that may be a negative regulator of the Wnt/beta-catenin signaling pathway. The encoded protein localizes to the nuclear membrane and has been implicated in the nuclear trafficking of the transcription repressors REST/NRSF and REST4. Mutations in this gene have been linked to progressive myoclonus epilepsy. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 3. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.24399793).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRICKLE1 | NM_153026.3 | c.1655G>A | p.Gly552Glu | missense_variant | 8/8 | ENST00000345127.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRICKLE1 | ENST00000345127.9 | c.1655G>A | p.Gly552Glu | missense_variant | 8/8 | 1 | NM_153026.3 | P1 | |
ENST00000547824.1 | n.1285C>T | non_coding_transcript_exon_variant | 1/2 | 1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Epilepsy, progressive myoclonic, 1B Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 30, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PRICKLE1 protein function. ClinVar contains an entry for this variant (Variation ID: 469507). This variant has not been reported in the literature in individuals affected with PRICKLE1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 552 of the PRICKLE1 protein (p.Gly552Glu). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
T;T;T;T;T;T;T;T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;M;M;M;M;M;M;M
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;.;N;.;N;.;.;N;.;N
REVEL
Benign
Sift
Uncertain
D;.;D;.;D;.;.;D;.;D
Sift4G
Uncertain
D;.;D;.;D;.;.;D;.;D
Polyphen
B;B;B;B;B;B;B;B;B;B
Vest4
MutPred
Gain of phosphorylation at S549 (P = 0.1348);Gain of phosphorylation at S549 (P = 0.1348);Gain of phosphorylation at S549 (P = 0.1348);Gain of phosphorylation at S549 (P = 0.1348);Gain of phosphorylation at S549 (P = 0.1348);Gain of phosphorylation at S549 (P = 0.1348);Gain of phosphorylation at S549 (P = 0.1348);Gain of phosphorylation at S549 (P = 0.1348);Gain of phosphorylation at S549 (P = 0.1348);Gain of phosphorylation at S549 (P = 0.1348);
MVP
MPC
0.49
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at