chr3-132559021-C-T
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_032169.5(ACAD11):c.2293G>A(p.Ala765Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,613,458 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
ACAD11
NM_032169.5 missense
NM_032169.5 missense
Scores
8
7
3
Clinical Significance
Conservation
PhyloP100: 6.90
Genes affected
ACAD11 (HGNC:30211): (acyl-CoA dehydrogenase family member 11) This gene encodes an acyl-CoA dehydrogenase enzyme with a preference for carbon chain lengths between 20 and 26. Naturally occurring read-through transcription occurs between the upstream gene NPHP3 (nephronophthisis 3 (adolescent)) and this gene. [provided by RefSeq, Aug 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.953
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACAD11 | NM_032169.5 | c.2293G>A | p.Ala765Thr | missense_variant | 20/20 | ENST00000264990.11 | |
NPHP3-ACAD11 | NR_037804.1 | n.6905G>A | non_coding_transcript_exon_variant | 45/45 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACAD11 | ENST00000264990.11 | c.2293G>A | p.Ala765Thr | missense_variant | 20/20 | 1 | NM_032169.5 | P1 | |
ACAD11 | ENST00000485198.5 | c.*774G>A | 3_prime_UTR_variant, NMD_transcript_variant | 18/18 | 1 | ||||
ACAD11 | ENST00000469042.5 | n.3079G>A | non_coding_transcript_exon_variant | 18/18 | 2 | ||||
ACAD11 | ENST00000496418.5 | n.2801G>A | non_coding_transcript_exon_variant | 19/19 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000658 AC: 10AN: 152032Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 250902Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135620
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GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461426Hom.: 0 Cov.: 30 AF XY: 0.0000165 AC XY: 12AN XY: 727016
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GnomAD4 genome AF: 0.0000658 AC: 10AN: 152032Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74258
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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 | Nov 10, 2022 | The c.2293G>A (p.A765T) alteration is located in exon 20 (coding exon 20) of the ACAD11 gene. This alteration results from a G to A substitution at nucleotide position 2293, causing the alanine (A) at amino acid position 765 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
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
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D;D;D
PROVEAN
Uncertain
D
REVEL
Pathogenic
Sift
Benign
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
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