17-7217796-G-GCGATGA
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PM4
The NM_001270447.2(ACADVL):c.111_116dupGATGAC(p.Thr39_Ala40insMetThr) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000108 in 1,383,176 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Genomes: not found (cov: 30)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
ACADVL
NM_001270447.2 disruptive_inframe_insertion
NM_001270447.2 disruptive_inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.245
Publications
0 publications found
Genes affected
DLG4 (HGNC:2903): (discs large MAGUK scaffold protein 4) This gene encodes a member of the membrane-associated guanylate kinase (MAGUK) family. It heteromultimerizes with another MAGUK protein, DLG2, and is recruited into NMDA receptor and potassium channel clusters. These two MAGUK proteins may interact at postsynaptic sites to form a multimeric scaffold for the clustering of receptors, ion channels, and associated signaling proteins. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
ACADVL (HGNC:92): (acyl-CoA dehydrogenase very long chain) The protein encoded by this gene is targeted to the inner mitochondrial membrane where it catalyzes the first step of the mitochondrial fatty acid beta-oxidation pathway. This acyl-Coenzyme A dehydrogenase is specific to long-chain and very-long-chain fatty acids. A deficiency in this gene product reduces myocardial fatty acid beta-oxidation and is associated with cardiomyopathy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
ACADVL Gene-Disease associations (from GenCC):
- very long chain acyl-CoA dehydrogenase deficiencyInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_001270447.2.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001270447.2. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DLG4 | NM_001365.5 | MANE Plus Clinical | c.159+439_159+444dupTCATCG | intron | N/A | NP_001356.1 | P78352-2 | ||
| ACADVL | NM_001270447.2 | c.111_116dupGATGAC | p.Thr39_Ala40insMetThr | disruptive_inframe_insertion | Exon 2 of 21 | NP_001257376.1 | P49748-3 | ||
| DLG4 | NM_001321074.1 | c.159+439_159+444dupTCATCG | intron | N/A | NP_001308003.1 | B9EGL1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DLG4 | ENST00000648172.9 | MANE Plus Clinical | c.159+439_159+444dupTCATCG | intron | N/A | ENSP00000497806.3 | P78352-2 | ||
| DLG4 | ENST00000399510.8 | TSL:1 | c.159+439_159+444dupTCATCG | intron | N/A | ENSP00000382428.3 | B9EGL1 | ||
| DLG4 | ENST00000491753.2 | TSL:2 | n.159+439_159+444dupTCATCG | intron | N/A | ENSP00000467897.2 | B7Z3U2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
30
GnomAD2 exomes AF: 0.00000779 AC: 1AN: 128368 AF XY: 0.0000142 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
128368
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000108 AC: 15AN: 1383176Hom.: 0 Cov.: 31 AF XY: 0.0000147 AC XY: 10AN XY: 682502 show subpopulations
GnomAD4 exome
AF:
AC:
15
AN:
1383176
Hom.:
Cov.:
31
AF XY:
AC XY:
10
AN XY:
682502
show subpopulations
African (AFR)
AF:
AC:
0
AN:
31594
American (AMR)
AF:
AC:
0
AN:
35680
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25162
East Asian (EAS)
AF:
AC:
0
AN:
35730
South Asian (SAS)
AF:
AC:
0
AN:
79234
European-Finnish (FIN)
AF:
AC:
0
AN:
33472
Middle Eastern (MID)
AF:
AC:
0
AN:
5692
European-Non Finnish (NFE)
AF:
AC:
15
AN:
1078728
Other (OTH)
AF:
AC:
0
AN:
57884
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.448
Heterozygous variant carriers
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
30
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Uncertain significance
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
-
1
-
Very long chain acyl-CoA dehydrogenase deficiency (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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