X-30665585-G-C
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001205019.2(GK):c.152+1G>C variant causes a splice donor, intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_001205019.2 splice_donor, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD4 exome Cov.: 17
GnomAD4 genome Cov.: 23
ClinVar
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
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Inborn glycerol kinase deficiency Pathogenic:1
This variant affects the canonical splice donor site of intron 2 and is therefore predicted to interfere with splicing and result in loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay (NMD). Multiple splice prediction tools suggest this variant is likely to interfere with normal splicing; however, to our knowledge, no RNA-base splicing analysis has been performed to clarify the effect of this alteration on splicing. This variant has not been previously reported or functionally characterized in the literature to our knowledge. Splice site variation in GK is an established mechanism of disease (PMID: 16549535). The c.152+1G>C variant is absent from the gnomAD population database and thus is presumed to be rare. Based on the available evidence, the c.152+1G>C variant is classified as Likely Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at