chr11-134253603-G-A
Variant names:
Variant summary
Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PVS1_StrongPS1_ModeratePM2
The NM_014384.3(ACAD8):c.3G>A(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.0000021 in 1,431,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
ACAD8
NM_014384.3 start_lost
NM_014384.3 start_lost
Scores
6
4
6
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 4.12
Publications
3 publications found
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]
THYN1 (HGNC:29560): (thymocyte nuclear protein 1) This gene encodes a protein that is highly conserved among vertebrates and plant species and may be involved in the induction of apoptosis. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 8 ACMG points.
PVS1
Start lost variant, next in-frame start position is after 5 pathogenic variants. Next in-frame start position is after 39 codons. Genomic position: 134256553. Lost 0.092 part of the original CDS.
PS1
Another start lost variant in NM_014384.3 (ACAD8) was described as [Likely_pathogenic] in ClinVar as 566782
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000210 AC: 3AN: 1431656Hom.: 0 Cov.: 31 AF XY: 0.00000282 AC XY: 2AN XY: 710054 show subpopulations
GnomAD4 exome
AF:
AC:
3
AN:
1431656
Hom.:
Cov.:
31
AF XY:
AC XY:
2
AN XY:
710054
show subpopulations
African (AFR)
AF:
AC:
0
AN:
32924
American (AMR)
AF:
AC:
0
AN:
41122
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25526
East Asian (EAS)
AF:
AC:
0
AN:
38152
South Asian (SAS)
AF:
AC:
0
AN:
82822
European-Finnish (FIN)
AF:
AC:
0
AN:
46752
Middle Eastern (MID)
AF:
AC:
0
AN:
5702
European-Non Finnish (NFE)
AF:
AC:
3
AN:
1099382
Other (OTH)
AF:
AC:
0
AN:
59274
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
PhyloP100
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;.
Polyphen
B;.
Vest4
MutPred
Gain of catalytic residue at M1 (P = 0.0657);Gain of catalytic residue at M1 (P = 0.0657);
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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