rs139457557
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4BP6
The NM_000016.6(ACADM):c.666C>A(p.Phe222Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000843 in 1,613,814 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000016.6 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ACADM | NM_000016.6 | c.666C>A | p.Phe222Leu | missense_variant | Exon 8 of 12 | ENST00000370841.9 | NP_000007.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000460 AC: 70AN: 152076Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000915 AC: 23AN: 251376Hom.: 1 AF XY: 0.0000442 AC XY: 6AN XY: 135878
GnomAD4 exome AF: 0.0000445 AC: 65AN: 1461620Hom.: 1 Cov.: 30 AF XY: 0.0000344 AC XY: 25AN XY: 727128
GnomAD4 genome AF: 0.000467 AC: 71AN: 152194Hom.: 0 Cov.: 33 AF XY: 0.000484 AC XY: 36AN XY: 74388
ClinVar
Submissions by phenotype
Medium-chain acyl-coenzyme A dehydrogenase deficiency Uncertain:2Benign:1
- -
The ACADM c.666C>A; p.Phe222Leu variant (rs139457557), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 582928). This variant is found in the African population with an allele frequency of 0.14% (35/24952 alleles, including one homozygote) in the Genome Aggregation Database (v2.1.1). Computational analyses predict that this variant is deleterious (REVEL: 0.708). Due to limited information, the clinical significance of the p.Phe222Leu variant is uncertain at this time. -
- -
Inborn genetic diseases Uncertain:1
The p.F222L variant (also known as c.666C>A), located in coding exon 8 of the ACADM gene, results from a C to A substitution at nucleotide position 666. The phenylalanine at codon 222 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at