rs781672373
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_153026.3(PRICKLE1):c.2089C>T(p.Pro697Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,613,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P697P) has been classified as Likely benign.
Frequency
Consequence
NM_153026.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRICKLE1 | NM_153026.3 | c.2089C>T | p.Pro697Ser | missense_variant | 8/8 | ENST00000345127.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRICKLE1 | ENST00000345127.9 | c.2089C>T | p.Pro697Ser | missense_variant | 8/8 | 1 | NM_153026.3 | P1 | |
ENST00000547824.1 | n.851G>A | non_coding_transcript_exon_variant | 1/2 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152098Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251440Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135894
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461876Hom.: 0 Cov.: 34 AF XY: 0.0000206 AC XY: 15AN XY: 727240
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152098Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74306
ClinVar
Submissions by phenotype
Epilepsy, progressive myoclonic, 1B Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 28, 2021 | This sequence change replaces proline with serine at codon 697 of the PRICKLE1 protein (p.Pro697Ser). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs781672373, ExAC 0.006%). This variant has not been reported in the literature in individuals affected with PRICKLE1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at