rs121908421

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5

The NM_014384.3(ACAD8):​c.867C>A​(p.His289Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

ACAD8
NM_014384.3 missense

Scores

3
5
11

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 0.0690
Variant links:
Genes affected
ACAD8 (HGNC:87): (acyl-CoA dehydrogenase family member 8) This gene encodes 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. The encoded protein is a mitochondrial enzyme that functions in catabolism of the branched-chain amino acid valine. Defects in this gene are the cause of isobutyryl-CoA dehydrogenase deficiency.[provided by RefSeq, Nov 2009]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.805
PP5
Variant 11-134261300-C-A is Pathogenic according to our data. Variant chr11-134261300-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 5358.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-134261300-C-A is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ACAD8NM_014384.3 linkuse as main transcriptc.867C>A p.His289Gln missense_variant 8/11 ENST00000281182.9 NP_055199.1 Q9UKU7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ACAD8ENST00000281182.9 linkuse as main transcriptc.867C>A p.His289Gln missense_variant 8/111 NM_014384.3 ENSP00000281182.5 Q9UKU7-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Deficiency of isobutyryl-CoA dehydrogenase Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMFeb 01, 2007- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.28
BayesDel_addAF
Pathogenic
0.35
D
BayesDel_noAF
Pathogenic
0.27
CADD
Benign
2.0
DANN
Benign
0.65
DEOGEN2
Uncertain
0.55
D;.
Eigen
Benign
-0.77
Eigen_PC
Benign
-0.60
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Uncertain
0.95
D;D
M_CAP
Benign
0.063
D
MetaRNN
Pathogenic
0.81
D;D
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
-2.9
N;.
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
1.9
N;N
REVEL
Uncertain
0.52
Sift
Benign
1.0
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.0090
B;.
Vest4
0.77
MutPred
0.85
Gain of relative solvent accessibility (P = 0.2363);.;
MVP
0.93
MPC
0.15
ClinPred
0.22
T
GERP RS
0.068
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.53
gMVP
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs121908421; hg19: chr11-134131194; API