19-7630571-A-G
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1_StrongPM2PP5_Very_Strong
The NM_001171155.2(PET100):c.28-2A>G variant causes a splice acceptor, intron change. The variant allele was found at a frequency of 0.00000217 in 1,384,080 control chromosomes in the GnomAD database, with no homozygous occurrence. 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_001171155.2 splice_acceptor, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PET100 | NM_001171155.2 | c.28-2A>G | splice_acceptor_variant, intron_variant | Intron 1 of 3 | ENST00000594797.6 | NP_001164626.1 | ||
STXBP2 | NM_001414484.1 | c.-170-2A>G | splice_acceptor_variant, intron_variant | Intron 1 of 20 | NP_001401413.1 | |||
PET100 | NR_033242.2 | n.69-2A>G | splice_acceptor_variant, intron_variant | Intron 1 of 4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PET100 | ENST00000594797.6 | c.28-2A>G | splice_acceptor_variant, intron_variant | Intron 1 of 3 | 1 | NM_001171155.2 | ENSP00000470539.1 | |||
ENSG00000268400 | ENST00000698368.1 | n.28-2A>G | splice_acceptor_variant, intron_variant | Intron 1 of 19 | ENSP00000513686.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000217 AC: 3AN: 1384080Hom.: 0 Cov.: 31 AF XY: 0.00000293 AC XY: 2AN XY: 683064
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
This sequence change affects an acceptor splice site in intron 1 of the PET100 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PET100 are known to be pathogenic (PMID: 24462369, 25293719, 31406627). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PET100-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. -
Mitochondrial complex 4 deficiency, nuclear type 12 Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at