ACAD9 p.Ser2Arg

Variant names:

• chr3-128879695-A-C
• NM_014049.5:c.4A>C
• ACAD9 p.Ser2Arg

Your query was ambiguous. Multiple possible variants found:

• chr3-128879695-A-C
• chr3-128879697-C-A
• chr3-128879697-C-G
• chr3-128879695-AGC-CGT
• chr3-128879695-AGC-CGA
• chr3-128879695-AGC-CGG

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014049.5(ACAD9):​c.4A>C​(p.Ser2Arg) variant causes a missense 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S2I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ACAD9 NM_014049.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.393
• Publications: 0 publications found

Genes affected

ACAD9 (HGNC:21497): (acyl-CoA dehydrogenase family member 9) This gene encodes a member of the acyl-CoA dehydrogenase family. Members of this family of proteins localize to the mitochondria and catalyze the rate-limiting step in the beta-oxidation of fatty acyl-CoA. The encoded protein is specifically active toward palmitoyl-CoA and long-chain unsaturated substrates. Mutations in this gene cause acyl-CoA dehydrogenase family member type 9 deficiency. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Mar 2010]

ACAD9-DT (HGNC:56086): (ACAD9 divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34914678).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014049.5. 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
	ACAD9	NM_014049.5	MANE Select	c.4A>C	p.Ser2Arg	missense	Exon 1 of 18	NP_054768.2
	ACAD9	NM_001410805.1		c.-272A>C		5_prime_UTR	Exon 1 of 17	NP_001397734.1	Q9H9W4
	ACAD9	NR_033426.2		n.76A>C		non_coding_transcript_exon	Exon 1 of 18

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACAD9	ENST00000308982.12	TSL:1 MANE Select	c.4A>C	p.Ser2Arg	missense	Exon 1 of 18	ENSP00000312618.7	Q9H845
	ACAD9	ENST00000681367.1		c.4A>C	p.Ser2Arg	missense	Exon 1 of 19	ENSP00000505309.1	A0A7P0T8U3
	ACAD9	ENST00000680636.1		c.4A>C	p.Ser2Arg	missense	Exon 1 of 18	ENSP00000504886.1	A0A7P0T7Z1

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
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.48	T
M_CAP	Pathogenic	0.37	D
MetaRNN	Benign	0.35	T
MetaSVM	Uncertain	0.13	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.39
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.29	N
REVEL	Uncertain	0.31
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.017	D
PromoterAI		-0.055	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.098
gMVP		0.48
Mutation Taster		=91/9	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-128598538;