12-111729820-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_025247.6(ACAD10):c.1258C>T(p.Arg420Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,613,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000025 ( 0 hom. )
Consequence
ACAD10
NM_025247.6 missense
NM_025247.6 missense
Scores
2
4
11
Clinical Significance
Conservation
PhyloP100: 2.00
Genes affected
ACAD10 (HGNC:21597): (acyl-CoA dehydrogenase family member 10) This gene encodes a member of the acyl-CoA dehydrogenase family of enzymes (ACADs), which participate in the beta-oxidation of fatty acids in mitochondria. The encoded enzyme contains a hydrolase domain at the N-terminal portion, a serine/threonine protein kinase catlytic domain in the central region, and a conserved ACAD domain at the C-terminus. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Nov 2008]
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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;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.28066018).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACAD10 | NM_025247.6 | c.1258C>T | p.Arg420Cys | missense_variant | 10/21 | ENST00000313698.9 | |
ACAD10 | NM_001136538.2 | c.1351C>T | p.Arg451Cys | missense_variant | 11/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACAD10 | ENST00000313698.9 | c.1258C>T | p.Arg420Cys | missense_variant | 10/21 | 1 | NM_025247.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152158Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000478 AC: 12AN: 251114Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135686
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GnomAD4 exome AF: 0.0000253 AC: 37AN: 1461570Hom.: 0 Cov.: 31 AF XY: 0.0000358 AC XY: 26AN XY: 727042
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152276Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74468
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 05, 2022 | The c.1351C>T (p.R451C) alteration is located in exon 11 (coding exon 10) of the ACAD10 gene. This alteration results from a C to T substitution at nucleotide position 1351, causing the arginine (R) at amino acid position 451 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
0.51
.;.;P
Vest4
MutPred
Gain of catalytic residue at P419 (P = 0.0012);.;Gain of catalytic residue at P419 (P = 0.0012);
MVP
MPC
0.41
ClinPred
D
GERP RS
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