12-42459667-C-T
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_153026.3(PRICKLE1):c.*142G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000025 in 799,058 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 (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000025 ( 0 hom. )
Consequence
PRICKLE1
NM_153026.3 3_prime_UTR
NM_153026.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.469
Publications
0 publications found
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]
PPHLN1 (HGNC:19369): (periphilin 1) The protein encoded by this gene is one of the several proteins that become sequentially incorporated into the cornified cell envelope during the terminal differentiation of keratinocyte at the outer layers of epidermis. This protein interacts with periplakin, which is known as a precursor of the cornified cell envelope. The cellular localization pattern and insolubility of this protein suggest that it may play a role in epithelial differentiation and contribute to epidermal integrity and barrier formation. Multiple alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| PRICKLE1 | NM_153026.3 | c.*142G>A | 3_prime_UTR_variant | Exon 8 of 8 | ENST00000345127.9 | NP_694571.2 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000250 AC: 2AN: 799058Hom.: 0 Cov.: 11 AF XY: 0.00000479 AC XY: 2AN XY: 417656 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
799058
Hom.:
Cov.:
11
AF XY:
AC XY:
2
AN XY:
417656
show subpopulations
African (AFR)
AF:
AC:
0
AN:
19724
American (AMR)
AF:
AC:
0
AN:
35726
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
18566
East Asian (EAS)
AF:
AC:
0
AN:
36794
South Asian (SAS)
AF:
AC:
0
AN:
62116
European-Finnish (FIN)
AF:
AC:
0
AN:
46702
Middle Eastern (MID)
AF:
AC:
0
AN:
2704
European-Non Finnish (NFE)
AF:
AC:
2
AN:
538624
Other (OTH)
AF:
AC:
0
AN:
38102
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.550
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
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
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
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
Publications
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