rs770961747
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2PP5_ModerateBP4BP7
The NM_000018.4(ACADVL):c.552C>A(p.Ile184=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. I184I) has been classified as Likely benign.
Frequency
Consequence
NM_000018.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACADVL | NM_000018.4 | c.552C>A | p.Ile184= | synonymous_variant | 7/20 | ENST00000356839.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACADVL | ENST00000356839.10 | c.552C>A | p.Ile184= | synonymous_variant | 7/20 | 1 | NM_000018.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461794Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727204
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Very long chain acyl-CoA dehydrogenase deficiency Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Victorian Clinical Genetics Services, Murdoch Childrens Research Institute | Jun 24, 2022 | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with VLCAD deficiency (MIM# 201475). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0210 - Splice site variant proven to affect splicing of the transcript with a known effect on protein sequence. Fibroblasts of this proband were analysed using RNAseq and allelic specific expression was performed, showing that this variant causes an out-of-frame exon 7 skipping resulting in NMD (Rare Diseases Now Research Project, individual RDN0001-00). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0311 - An alternative nucleotide change is present in gnomAD (v2) at a frequency of 0.00003181 (8 heterozygotes, 0 homozygotes). (SB) 0701 - Other variants predicted to result in NMD comparable to the one identified in this case have very strong previous evidence for pathogenicity (DECIPHER). (SP) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1005 - Clinically accredited laboratory assay specific to gene product shows abnormal protein function. Analysis of this proband’s Guthrie card sample has shown an acyl carnitine profile consistent with VLCAD deficiency (VCGS #19M500295). (SP) 1205 - This variant has been shown to be maternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.