chr10-123034470-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001609.4(ACADSB):c.157C>T(p.Pro53Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000154 in 1,612,328 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P53P) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00017 ( 0 hom. )
Consequence
ACADSB
NM_001609.4 missense
NM_001609.4 missense
Scores
1
11
7
Clinical Significance
Conservation
PhyloP100: 4.92
Genes affected
ACADSB (HGNC:91): (acyl-CoA dehydrogenase short/branched chain) Short/branched chain acyl-CoA dehydrogenase(ACADSB) is a member of the acyl-CoA dehydrogenase family of enzymes that catalyze the dehydrogenation of acyl-CoA derivatives in the metabolism of fatty acids or branch chained amino acids. Substrate specificity is the primary characteristic used to define members of this gene family. The ACADSB gene product has the greatest activity towards the short branched chain acyl-CoA derivative, (S)-2-methylbutyryl-CoA, but also reacts significantly with other 2-methyl branched chain substrates and with short straight chain acyl-CoAs. The cDNA encodes for a mitochondrial precursor protein which is cleaved upon mitochondrial import and predicted to yield a mature peptide of approximately 43.7-KDa. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACADSB | NM_001609.4 | c.157C>T | p.Pro53Ser | missense_variant | 2/11 | ENST00000358776.7 | |
ACADSB | NM_001330174.3 | c.-49C>T | 5_prime_UTR_variant | 2/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACADSB | ENST00000358776.7 | c.157C>T | p.Pro53Ser | missense_variant | 2/11 | 1 | NM_001609.4 | P1 | |
ACADSB | ENST00000368869.8 | c.-49C>T | 5_prime_UTR_variant | 2/10 | 2 | ||||
ACADSB | ENST00000411816.2 | n.174C>T | non_coding_transcript_exon_variant | 2/4 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152188Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000761 AC: 19AN: 249714Hom.: 1 AF XY: 0.0000740 AC XY: 10AN XY: 135112
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GnomAD4 exome AF: 0.000165 AC: 241AN: 1460022Hom.: 0 Cov.: 31 AF XY: 0.000146 AC XY: 106AN XY: 726422
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GnomAD4 genome AF: 0.0000460 AC: 7AN: 152306Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74474
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Deficiency of 2-methylbutyryl-CoA dehydrogenase Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 21, 2022 | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 53 of the ACADSB protein (p.Pro53Ser). This variant is present in population databases (rs150022323, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of ACADSB-related conditions (PMID: 31785789). ClinVar contains an entry for this variant (Variation ID: 1514895). 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: "Benign"; 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 02, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Uncertain
D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Benign
T
Sift4G
Uncertain
T
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at