3-132575837-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_032169.5(ACAD11):c.1936G>A(p.Ala646Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000211 in 1,614,016 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )
Consequence
ACAD11
NM_032169.5 missense
NM_032169.5 missense
Scores
6
6
6
Clinical Significance
Conservation
PhyloP100: 4.79
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 Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.748
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACAD11 | NM_032169.5 | c.1936G>A | p.Ala646Thr | missense_variant | 17/20 | ENST00000264990.11 | |
NPHP3-ACAD11 | NR_037804.1 | n.6548G>A | non_coding_transcript_exon_variant | 42/45 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACAD11 | ENST00000264990.11 | c.1936G>A | p.Ala646Thr | missense_variant | 17/20 | 1 | NM_032169.5 | P1 | |
ACAD11 | ENST00000485198.5 | c.*417G>A | 3_prime_UTR_variant, NMD_transcript_variant | 15/18 | 1 | ||||
ACAD11 | ENST00000496418.5 | n.2444G>A | non_coding_transcript_exon_variant | 16/19 | 2 | ||||
ACAD11 | ENST00000469042.5 | n.2787+1107G>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152078Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251046Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135644
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GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461820Hom.: 0 Cov.: 31 AF XY: 0.0000234 AC XY: 17AN XY: 727208
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152196Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74420
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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 | Mar 20, 2024 | The c.1936G>A (p.A646T) alteration is located in exon 17 (coding exon 17) of the ACAD11 gene. This alteration results from a G to A substitution at nucleotide position 1936, causing the alanine (A) at amino acid position 646 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
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D;D;D
PROVEAN
Benign
N
REVEL
Pathogenic
Sift
Benign
T
Sift4G
Uncertain
T
Polyphen
B
Vest4
MutPred
Loss of MoRF binding (P = 0.1289);
MVP
MPC
ClinPred
T
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