rs1057520141
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_153026.3(PRICKLE1):āc.2037A>Cā(p.Arg679Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 0.0000021 ( 0 hom. )
Consequence
PRICKLE1
NM_153026.3 missense
NM_153026.3 missense
Scores
1
8
9
Clinical Significance
Conservation
PhyloP100: -0.961
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 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.26407582).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRICKLE1 | NM_153026.3 | c.2037A>C | p.Arg679Ser | missense_variant | 8/8 | ENST00000345127.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRICKLE1 | ENST00000345127.9 | c.2037A>C | p.Arg679Ser | missense_variant | 8/8 | 1 | NM_153026.3 | P1 | |
ENST00000547824.1 | n.903T>G | non_coding_transcript_exon_variant | 1/2 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152174Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251468Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135912
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461892Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2AN XY: 727246
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152174Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74338
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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 submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Nov 07, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Uncertain
D;D;D;D;D;D;D;D;D;D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Uncertain
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
D;.;D;.;D;.;.;D;.;D
REVEL
Uncertain
Sift
Uncertain
D;.;D;.;D;.;.;D;.;D
Sift4G
Uncertain
D;.;D;.;D;.;.;D;.;D
Polyphen
P;P;P;P;P;P;P;P;P;P
Vest4
MutPred
Gain of phosphorylation at R679 (P = 2e-04);Gain of phosphorylation at R679 (P = 2e-04);Gain of phosphorylation at R679 (P = 2e-04);Gain of phosphorylation at R679 (P = 2e-04);Gain of phosphorylation at R679 (P = 2e-04);Gain of phosphorylation at R679 (P = 2e-04);Gain of phosphorylation at R679 (P = 2e-04);Gain of phosphorylation at R679 (P = 2e-04);Gain of phosphorylation at R679 (P = 2e-04);Gain of phosphorylation at R679 (P = 2e-04);
MVP
MPC
1.2
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at