10-123051188-T-TTA
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_001609.4(ACADSB):c.1128+2_1128+3insTA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001609.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ACADSB | NM_001609.4 | c.1128+2_1128+3insTA | splice_region_variant, intron_variant | Intron 9 of 10 | ENST00000358776.7 | NP_001600.1 | ||
ACADSB | NM_001330174.3 | c.822+2_822+3insTA | splice_region_variant, intron_variant | Intron 8 of 9 | NP_001317103.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ACADSB | ENST00000358776.7 | c.1128+2_1128+3insTA | splice_region_variant, intron_variant | Intron 9 of 10 | 1 | NM_001609.4 | ENSP00000357873.3 | |||
ACADSB | ENST00000368869.8 | c.822+2_822+3insTA | splice_region_variant, intron_variant | Intron 8 of 9 | 2 | ENSP00000357862.4 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 0AN: 76456Hom.: 0 Cov.: 0 FAILED QC
GnomAD4 exome Cov.: 0
GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 76456Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 34186
ClinVar
Submissions by phenotype
Deficiency of 2-methylbutyryl-CoA dehydrogenase Uncertain:1
This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 9 of the ACADSB gene. It does not directly change the encoded amino acid sequence of the ACADSB protein, but it affects a nucleotide within the consensus splice site of the intron. Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with ACADSB-related disease. 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