rs875989865

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PS1_ModeratePM2

The NM_000016.6(ACADM):​c.-6_6delGCCAACATGGCAinsACCCCGAAGG​(p.Met1fs) variant causes a frameshift, start lost change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

ACADM
NM_000016.6 frameshift, start_lost

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.58
Variant links:
Genes affected
ACADM (HGNC:89): (acyl-CoA dehydrogenase medium chain) This gene encodes the medium-chain specific (C4 to C12 straight chain) acyl-Coenzyme A dehydrogenase. The homotetramer enzyme catalyzes the initial step of the mitochondrial fatty acid beta-oxidation pathway. Defects in this gene cause medium-chain acyl-CoA dehydrogenase deficiency, a disease characterized by hepatic dysfunction, fasting hypoglycemia, and encephalopathy, which can result in infantile death. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 243 pathogenic variants in the truncated region.
PS1
Another start lost variant in NM_000016.6 (ACADM) was described as [Likely_pathogenic] in ClinVar as 555765
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ACADMNM_000016.6 linkc.-6_6delGCCAACATGGCAinsACCCCGAAGG p.Met1fs frameshift_variant, start_lost Exon 1 of 12 ENST00000370841.9 NP_000007.1 P11310-1A0A0S2Z366
ACADMNM_000016.6 linkc.-6_6delGCCAACATGGCAinsACCCCGAAGG 5_prime_UTR_variant Exon 1 of 12 ENST00000370841.9 NP_000007.1 P11310-1A0A0S2Z366

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ACADMENST00000370841.9 linkc.-6_6delGCCAACATGGCAinsACCCCGAAGG p.Met1fs frameshift_variant, start_lost Exon 1 of 12 1 NM_000016.6 ENSP00000359878.5 P11310-1
ACADMENST00000370841 linkc.-6_6delGCCAACATGGCAinsACCCCGAAGG 5_prime_UTR_variant Exon 1 of 12 1 NM_000016.6 ENSP00000359878.5 P11310-1

Frequencies

GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs875989865; hg19: chr1-76190467; API