ENST00000541113:c.-304A>G

Variant names:

• chr1-75724484-A-G
• rs886046521
• ENST00000541113.6:c.-304A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000541113.6(ACADM):​c.-304A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000294 in 238,460 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000033 (0 hom.)
• Consequence: ACADM ENST00000541113.6 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.40
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000541113.6. 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.-304A>G		upstream_gene	N/A	NP_000007.1	A0A0S2Z366
	ACADM	NM_001286043.2		c.-304A>G		upstream_gene	N/A	NP_001272972.1	Q5T4U5
	ACADM	NM_001127328.3		c.-304A>G		upstream_gene	N/A	NP_001120800.1	P11310-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACADM	ENST00000541113.6	TSL:1	c.-304A>G		5_prime_UTR	Exon 1 of 11	ENSP00000442324.2	F6YB23
	ACADM	ENST00000680805.1		c.-304A>G		5_prime_UTR	Exon 1 of 11	ENSP00000505447.1	A0A7P0T932
	ACADM	ENST00000680964.1		c.-304A>G		5_prime_UTR	Exon 1 of 12	ENSP00000505961.1	A0A7P0TB51

Frequencies

GnomAD3 genomes AF: 0.0000272 AC: 4 AN: 147142 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000596

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000329 AC: 3 AN: 91318 Hom.: 0 Cov.: 0 AF XY: 0.0000211 AC XY: 1 AN XY: 47388

African (AFR) AF: 0.00 AC: 0 AN: 2742

American (AMR) AF: 0.00 AC: 0 AN: 2532

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3414

East Asian (EAS) AF: 0.00 AC: 0 AN: 8288

South Asian (SAS) AF: 0.00 AC: 0 AN: 2130

European-Finnish (FIN) AF: 0.000278 AC: 2 AN: 7188

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 502

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 58514

Other (OTH) AF: 0.000166 AC: 1 AN: 6008

GnomAD4 genome AF: 0.0000272 AC: 4 AN: 147142 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 71632

African (AFR) AF: 0.00 AC: 0 AN: 39816

American (AMR) AF: 0.00 AC: 0 AN: 14810

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3436

East Asian (EAS) AF: 0.00 AC: 0 AN: 4660

South Asian (SAS) AF: 0.00 AC: 0 AN: 4356

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9772

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 300

European-Non Finnish (NFE) AF: 0.0000596 AC: 4 AN: 67058

Other (OTH) AF: 0.00 AC: 0 AN: 2032

Alfa AF: 0.0000843 Hom.: 0

Bravo AF: 0.0000378

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	-0.92
CADD	Benign	1.4
DANN	Benign	0.55
PhyloP100		-1.4
PromoterAI		-0.024	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.23		Position offset: -5

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

Other links and lift over

dbSNP: rs886046521; hg19: chr1-76190169;