rs1237915800

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001270447.2(ACADVL):​c.67C>A​(p.Gln23Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,383,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 30)
Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

ACADVL
NM_001270447.2 missense

Scores

1
2
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.224
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06180513).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DLG4NM_001321075.3 linkc.-607G>T upstream_gene_variant ENST00000399506.9 NP_001308004.1 P78352-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DLG4ENST00000648172.8 linkc.159+487G>T intron_variant Intron 3 of 21 ENSP00000497806.3 P78352-2
DLG4ENST00000491753.2 linkn.159+487G>T intron_variant Intron 3 of 20 2 ENSP00000467897.2 B7Z3U2
DLG4ENST00000399506.9 linkc.-607G>T upstream_gene_variant 2 NM_001321075.3 ENSP00000382425.2 P78352-1

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
AF:
7.23e-7
AC:
1
AN:
1383176
Hom.:
0
Cov.:
31
AF XY:
0.00000147
AC XY:
1
AN XY:
682508
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.27e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.059
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
13
DANN
Benign
0.78
Eigen
Benign
-0.95
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.32
T
M_CAP
Uncertain
0.16
D
MetaRNN
Benign
0.062
T
MetaSVM
Uncertain
0.021
D
PROVEAN
Benign
-0.030
N
REVEL
Benign
0.25
Sift
Pathogenic
0.0
D
Vest4
0.12
MutPred
0.16
Gain of ubiquitination at Q23 (P = 0.0276);
MVP
0.51
MPC
0.25
ClinPred
0.055
T
GERP RS
-2.2
gMVP
0.46

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-7121073; API