rs144540943
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The NM_145239.3(PRRT2):c.1013T>A(p.Val338Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000125 in 1,594,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V338A) has been classified as Likely benign.
Frequency
Consequence
NM_145239.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRRT2 | NM_145239.3 | c.1013T>A | p.Val338Glu | missense_variant, splice_region_variant | 4/4 | ENST00000358758.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRRT2 | ENST00000358758.12 | c.1013T>A | p.Val338Glu | missense_variant, splice_region_variant | 4/4 | 1 | NM_145239.3 | P1 | |
MVP-DT | ENST00000569039.5 | n.246-4455A>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000671 AC: 1AN: 149012Hom.: 0 Cov.: 32
GnomAD4 exome AF: 6.92e-7 AC: 1AN: 1445674Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1AN XY: 719626
GnomAD4 genome ? AF: 0.00000671 AC: 1AN: 149012Hom.: 0 Cov.: 32 AF XY: 0.0000137 AC XY: 1AN XY: 72728
ClinVar
Submissions by phenotype
Episodic kinesigenic dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 11, 2022 | This sequence change replaces valine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 338 of the PRRT2 protein (p.Val338Glu). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 1304099). This variant has not been reported in the literature in individuals affected with PRRT2-related conditions. This variant is not present in population databases (gnomAD no frequency). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 16, 2019 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at