rs199893979
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_153026.3(PRICKLE1):āc.2064T>Cā(p.Asn688=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000134 in 1,613,992 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 Likely benign (ā ā ).
Frequency
Genomes: š 0.000079 ( 0 hom., cov: 32)
Exomes š: 0.00014 ( 0 hom. )
Consequence
PRICKLE1
NM_153026.3 synonymous
NM_153026.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.172
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 Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
?
Variant 12-42460241-A-G is Benign according to our data. Variant chr12-42460241-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 385233.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.172 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRICKLE1 | NM_153026.3 | c.2064T>C | p.Asn688= | synonymous_variant | 8/8 | ENST00000345127.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRICKLE1 | ENST00000345127.9 | c.2064T>C | p.Asn688= | synonymous_variant | 8/8 | 1 | NM_153026.3 | P1 | |
ENST00000547824.1 | n.876A>G | non_coding_transcript_exon_variant | 1/2 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000789 AC: 12AN: 152102Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000115 AC: 29AN: 251452Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135904
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GnomAD4 exome AF: 0.000140 AC: 205AN: 1461890Hom.: 0 Cov.: 34 AF XY: 0.000131 AC XY: 95AN XY: 727244
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GnomAD4 genome ? AF: 0.0000789 AC: 12AN: 152102Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7AN XY: 74298
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 27, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Epilepsy, progressive myoclonic, 1B Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 11, 2023 | - - |
PRICKLE1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 27, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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