1-75732737-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001286044.2(ACADM):​c.-174G>T variant causes a 5 prime UTR premature start codon gain change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

ACADM
NM_001286044.2 5_prime_UTR_premature_start_codon_gain

Scores

12
6
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.18
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 Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.851

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ACADMNM_000016.6 linkuse as main transcriptc.212G>T p.Gly71Val missense_variant 3/12 ENST00000370841.9 NP_000007.1 P11310-1A0A0S2Z366

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ACADMENST00000370841.9 linkuse as main transcriptc.212G>T p.Gly71Val missense_variant 3/121 NM_000016.6 ENSP00000359878.5 P11310-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.74
BayesDel_addAF
Pathogenic
0.54
D
BayesDel_noAF
Pathogenic
0.54
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.83
D;D;D;.
Eigen
Pathogenic
0.88
Eigen_PC
Pathogenic
0.84
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.97
D;D;D;D
M_CAP
Pathogenic
0.58
D
MetaRNN
Pathogenic
0.85
D;D;D;D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Pathogenic
3.7
.;H;.;.
PrimateAI
Uncertain
0.54
T
PROVEAN
Pathogenic
-6.6
D;D;D;D
REVEL
Pathogenic
0.90
Sift
Uncertain
0.010
D;D;D;D
Sift4G
Uncertain
0.041
D;D;D;D
Polyphen
1.0
D;D;D;D
Vest4
0.59
MutPred
0.49
.;Gain of catalytic residue at G71 (P = 0.0451);Gain of catalytic residue at G71 (P = 0.0451);.;
MVP
0.99
MPC
0.80
ClinPred
1.0
D
GERP RS
5.6
Varity_R
0.98
gMVP
0.83

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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: rs1553122943; hg19: chr1-76198422; API