rs199963793
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001609.4(ACADSB):āc.1186A>Gā(p.Lys396Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000198 in 1,613,930 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K396T) has been classified as Likely benign.
Frequency
Consequence
NM_001609.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACADSB | NM_001609.4 | c.1186A>G | p.Lys396Glu | missense_variant | 10/11 | ENST00000358776.7 | |
ACADSB | NM_001330174.3 | c.880A>G | p.Lys294Glu | missense_variant | 9/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACADSB | ENST00000358776.7 | c.1186A>G | p.Lys396Glu | missense_variant | 10/11 | 1 | NM_001609.4 | P1 | |
ACADSB | ENST00000368869.8 | c.880A>G | p.Lys294Glu | missense_variant | 9/10 | 2 | |||
ACADSB | ENST00000541070.1 | n.358A>G | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152174Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000139 AC: 35AN: 251424Hom.: 0 AF XY: 0.000155 AC XY: 21AN XY: 135882
GnomAD4 exome AF: 0.000208 AC: 304AN: 1461756Hom.: 0 Cov.: 32 AF XY: 0.000221 AC XY: 161AN XY: 727184
GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152174Hom.: 0 Cov.: 33 AF XY: 0.0000942 AC XY: 7AN XY: 74334
ClinVar
Submissions by phenotype
Deficiency of 2-methylbutyryl-CoA dehydrogenase Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2021 | This sequence change replaces lysine with glutamic acid at codon 396 of the ACADSB protein (p.Lys396Glu). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is present in population databases (rs199963793, ExAC 0.01%). This missense change has been observed in individual(s) with clinical features of short/branched chain acyl-CoA dehydrogenase deficiency (PMID: 30626930; Invitae). ClinVar contains an entry for this variant (Variation ID: 377304). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Feb 03, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at