NM_145239.3:c.-66+1G>A
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_145239.3(PRRT2):c.-66+1G>A variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,220 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_145239.3 splice_donor, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRRT2 | ENST00000358758.12 | c.-66+1G>A | splice_donor_variant, intron_variant | Intron 1 of 3 | 1 | NM_145239.3 | ENSP00000351608.7 | |||
ENSG00000280893 | ENST00000609618.2 | n.-66+1G>A | splice_donor_variant, intron_variant | Intron 1 of 5 | 5 | ENSP00000476774.2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152220Hom.: 0 Cov.: 31
GnomAD4 exome Cov.: 0
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152220Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1AN XY: 74356
ClinVar
Submissions by phenotype
not provided Uncertain:1
c.-66+1 G>A: IVS1+1 G>A in intron 1 of the PRRT2 gene (NM_145239.2)A variant of unknown significance has been identified in the PRRT2 gene. The c.-66+1 G>A variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The c.-66+1 G>A variant destroys the canonical splice donor site of non-coding exon 1, either leading to the inclusion of abnormal sequence into the 5' UTR or deletion of sequence normally included in the 5' UTR. However, to our knowledge, no regulatory mutations have been reported in the PRRT2 gene. Additionally, in the absence of RNA/functional studies, the actual effect of the c.-66+1 G>A sequence change is unknown. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in EPILEPSY panel(s). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at