rs780504551

Variant names:

• chr1-75749553-A-G
• rs780504551
• NM_000016.6:c.843A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-75749553-A-G
• chr1-75749553-A-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000016.6(ACADM):​c.843A>G​(p.Arg281Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign 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_000016.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.968
• 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: G2P, ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=0.968 with no splicing effect.

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.843A>G	p.Arg281Arg	synonymous	Exon 9 of 12	NP_000007.1	A0A0S2Z366
	ACADM	NM_001286043.2		c.942A>G	p.Arg314Arg	synonymous	Exon 10 of 13	NP_001272972.1	Q5T4U5
	ACADM	NM_001127328.3		c.855A>G	p.Arg285Arg	synonymous	Exon 9 of 12	NP_001120800.1	P11310-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACADM	ENST00000370841.9	TSL:1 MANE Select	c.843A>G	p.Arg281Arg	synonymous	Exon 9 of 12	ENSP00000359878.5	P11310-1
	ACADM	ENST00000370834.9	TSL:1	c.942A>G	p.Arg314Arg	synonymous	Exon 10 of 13	ENSP00000359871.5	Q5T4U5
	ACADM	ENST00000420607.6	TSL:1	c.855A>G	p.Arg285Arg	synonymous	Exon 9 of 12	ENSP00000409612.2	P11310-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	8.8
DANN	Benign	0.70
PhyloP100		0.97
Mutation Taster		=87/13	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: rs780504551; hg19: chr1-76215238;