rs779901247
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM5
The NM_000018.4(ACADVL):āc.1504C>Gā(p.Leu502Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L502P) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000018.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152152Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461734Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 727172
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74302
ClinVar
Submissions by phenotype
Very long chain acyl-CoA dehydrogenase deficiency Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine | Nov 01, 2019 | The NM_000018.3:c.1504C>G (NP_000009.1:p.Leu502Val) [GRCH38: NC_000017.11:g.7224215C>G] variant in ACADVL gene is interpretated to be Uncertain Significance based on ACMG guidelines (PMID: 25741868). This variant has been reported. This variant meets the following evidence codes reported in the ACMG guidelines: PM5, PP3 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Nov 16, 2021 | NM_000018.3(ACADVL):c.1504C>G(L502V) is a missense variant classified as a variant of uncertain significance in the context of very long chain acyl-CoA dehydrogenase deficiency. L502V has been observed in cases with relevant disease (PMID: 26385305, 27209629, 23867825, 23418865). Functional assessments of this variant are not available in the literature. L502V has not been observed in population frequency databases. In summary, there is insufficient evidence to classify NM_000018.3(ACADVL):c.1504C>G(L502V) as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 31, 2022 | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 502 of the ACADVL protein (p.Leu502Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with very long-chain acyl-CoA dehydrogenase deficiency (PMID: 23867825, 27209629, 31031081). ClinVar contains an entry for this variant (Variation ID: 203586). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
not provided Pathogenic:1
Likely pathogenic, flagged submission | clinical testing | Eurofins Ntd Llc (ga) | Jul 06, 2015 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 21, 2025 | Variant summary: ACADVL c.1504C>G (p.Leu502Val) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 251238 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1504C>G has been reported in the literature in individuals diagnosed with Very Long Chain Acyl-CoA Dehydrogenase Deficiency by newborn screen with unclear clinical diagnoses (Erlingsson_2013, Pena_2016, Rovelli_2019). These report(s) do not provide unequivocal conclusions about association of the variant with Very Long Chain Acyl-CoA Dehydrogenase Deficiency. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 23867825, 27209629, 31031081). ClinVar contains an entry for this variant (Variation ID: 203586). Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 09, 2023 | The c.1504C>G (p.L502V) alteration is located in exon 15 (coding exon 15) of the ACADVL gene. This alteration results from a C to G substitution at nucleotide position 1504, causing the leucine (L) at amino acid position 502 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at