12-120727020-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_000017.4(ACADS):c.47-6C>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,613,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000017.4 splice_region, splice_polypyrimidine_tract, intron
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 |
---|---|---|---|---|---|---|---|
ACADS | NM_000017.4 | c.47-6C>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000242592.9 | |||
ACADS | NM_001302554.2 | c.47-6C>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACADS | ENST00000242592.9 | c.47-6C>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000017.4 | P1 | |||
ACADS | ENST00000411593.2 | c.47-6C>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 2 | |||||
ACADS | ENST00000539690.1 | n.159-6C>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152178Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251362Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135868
GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461802Hom.: 0 Cov.: 32 AF XY: 0.0000234 AC XY: 17AN XY: 727204
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74350
ClinVar
Submissions by phenotype
Deficiency of butyryl-CoA dehydrogenase Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 09, 2023 | This sequence change falls in intron 1 of the ACADS gene. It does not directly change the encoded amino acid sequence of the ACADS protein. This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has been observed in individual(s) with clinical features of short chain acyl-CoA dehydrogenase (SCAD) deficiency (PMID: 16926354). This variant is also known as IVS1-6C>A. ClinVar contains an entry for this variant (Variation ID: 550915). 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 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Mar 22, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at