rs780609527
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The NM_014384.3(ACAD8):c.734C>T(p.Ala245Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,612,464 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000019 ( 0 hom. )
Consequence
ACAD8
NM_014384.3 missense
NM_014384.3 missense
Scores
7
5
7
Clinical Significance
Conservation
PhyloP100: 7.85
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 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP6
?
Variant 11-134261072-C-T is Benign according to our data. Variant chr11-134261072-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 570341.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACAD8 | NM_014384.3 | c.734C>T | p.Ala245Val | missense_variant | 7/11 | ENST00000281182.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACAD8 | ENST00000281182.9 | c.734C>T | p.Ala245Val | missense_variant | 7/11 | 1 | NM_014384.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152178Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000972 AC: 24AN: 246900Hom.: 0 AF XY: 0.0000450 AC XY: 6AN XY: 133466
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GnomAD4 exome AF: 0.0000192 AC: 28AN: 1460286Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 726226
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152178Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74336
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 08, 2024 | The c.734C>T (p.A245V) alteration is located in exon 7 (coding exon 7) of the ACAD8 gene. This alteration results from a C to T substitution at nucleotide position 734, causing the alanine (A) at amino acid position 245 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Deficiency of isobutyryl-CoA dehydrogenase Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 04, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D
MetaSVM
Pathogenic
D
MutationAssessor
Benign
N;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
T
PROVEAN
Benign
N;N
REVEL
Pathogenic
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MutPred
Gain of MoRF binding (P = 0.1452);.;
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Score
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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