NM_000017.4:c.990C>A

Variant names:

• chr12-120738876-C-A
• rs3915
• NM_000017.4:c.990C>A

Variant summary

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

The NM_000017.4(ACADS):​c.990C>A​(p.Arg330Arg) 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. Synonymous variant affecting the same amino acid position (i.e. R330R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: ACADS NM_000017.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 34 publications found

Genes affected

ACADS (HGNC:90): (acyl-CoA dehydrogenase short chain) This gene encodes a tetrameric mitochondrial flavoprotein, which is a member of the acyl-CoA dehydrogenase family. This enzyme catalyzes the initial step of the mitochondrial fatty acid beta-oxidation pathway. Mutations in this gene have been associated with short-chain acyl-CoA dehydrogenase (SCAD) deficiency. Alternative splicing results in two variants which encode different isoforms. [provided by RefSeq, Oct 2014]

ACADS Gene-Disease associations (from GenCC):

• short chain acyl-CoA dehydrogenase deficiency

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

ENSG00000255946 (HGNC:):

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=-0.65).
• BP7: Synonymous conserved (PhyloP=-1.49 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000017.4. 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
	ACADS	NM_000017.4	MANE Select	c.990C>A	p.Arg330Arg	synonymous	Exon 8 of 10	NP_000008.1	P16219
	ACADS	NM_001302554.2		c.978C>A	p.Arg326Arg	synonymous	Exon 8 of 10	NP_001289483.1	E9PE82

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACADS	ENST00000242592.9	TSL:1 MANE Select	c.990C>A	p.Arg330Arg	synonymous	Exon 8 of 10	ENSP00000242592.4	P16219
	ACADS	ENST00000946559.1		c.990C>A	p.Arg330Arg	synonymous	Exon 8 of 10	ENSP00000616618.1
	ACADS	ENST00000893619.1		c.990C>A	p.Arg330Arg	synonymous	Exon 8 of 10	ENSP00000563678.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 70

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.013
DANN	Benign	0.84
PhyloP100		-1.5

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: rs3915; hg19: chr12-121176679;