NM_000016.6:c.-29T>C

Variant names:

• chr1-75724759-T-C
• rs763024539
• NM_000016.6:c.-29T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000016.6(ACADM):​c.-29T>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000274 in 1,534,788 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000011 (1 hom.)
• Consequence: ACADM NM_000016.6 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.65
• Publications: 0 publications found

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]

ACADM Gene-Disease associations (from GenCC):

• medium chain acyl-CoA dehydrogenase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), G2P

ENSG00000293044 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000016.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACADM	NM_000016.6	MANE Select	c.-29T>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 12	NP_000007.1	A0A0S2Z366
	ACADM	NM_000016.6	MANE Select	c.-29T>C		5_prime_UTR	Exon 1 of 12	NP_000007.1	A0A0S2Z366
	ACADM	NM_001286043.2		c.-29T>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 13	NP_001272972.1	Q5T4U5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACADM	ENST00000370841.9	TSL:1 MANE Select	c.-29T>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 12	ENSP00000359878.5	P11310-1
	ACADM	ENST00000370834.9	TSL:1	c.-29T>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 13	ENSP00000359871.5	Q5T4U5
	ACADM	ENST00000541113.6	TSL:1	c.-29T>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	ENSP00000442324.2	F6YB23

Frequencies

GnomAD3 genomes AF: 0.000177 AC: 27 AN: 152184 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000631 AC: 12 AN: 190180 AF XY: 0.0000482

Gnomad AFR exome AF: 0.0000881

Gnomad AMR exome AF: 0.000451

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000108 AC: 15 AN: 1382604 Hom.: 1 Cov.: 31 AF XY: 0.0000102 AC XY: 7 AN XY: 685278

African (AFR) AF: 0.0000347 AC: 1 AN: 28820

American (AMR) AF: 0.000343 AC: 12 AN: 35024

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23282

East Asian (EAS) AF: 0.00 AC: 0 AN: 33112

South Asian (SAS) AF: 0.00 AC: 0 AN: 76984

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51798

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5494

European-Non Finnish (NFE) AF: 9.33e-7 AC: 1 AN: 1071448

Other (OTH) AF: 0.0000177 AC: 1 AN: 56642

GnomAD4 genome AF: 0.000177 AC: 27 AN: 152184 Hom.: 0 Cov.: 32 AF XY: 0.000256 AC XY: 19 AN XY: 74350

African (AFR) AF: 0.0000241 AC: 1 AN: 41456

American (AMR) AF: 0.00170 AC: 26 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000144

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Medium-chain acyl-coenzyme A dehydrogenase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.27
DANN	Benign	0.55
PhyloP100		-2.6
PromoterAI		-0.0048	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=299/1	polymorphism

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

Other links and lift over

dbSNP: rs763024539; hg19: chr1-76190444;