3-128879708-T-C

Variant names:

• chr3-128879708-T-C
• rs879173625
• NM_014049.5:c.17T>C

Variant summary

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

The NM_014049.5(ACAD9):​c.17T>C​(p.Leu6Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. L6L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ACAD9 NM_014049.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.08
• 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 2 ACMG points.

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

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.17T>C	p.Leu6Pro	missense	Exon 1 of 18	NP_054768.2
	ACAD9	NM_001410805.1		c.-259T>C		5_prime_UTR	Exon 1 of 17	NP_001397734.1	Q9H9W4
	ACAD9	NR_033426.2		n.89T>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.17T>C	p.Leu6Pro	missense	Exon 1 of 18	ENSP00000312618.7	Q9H845
	ACAD9	ENST00000681367.1		c.17T>C	p.Leu6Pro	missense	Exon 1 of 19	ENSP00000505309.1	A0A7P0T8U3
	ACAD9	ENST00000680636.1		c.17T>C	p.Leu6Pro	missense	Exon 1 of 18	ENSP00000504886.1	A0A7P0T7Z1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.62	T
M_CAP	Pathogenic	0.50	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Uncertain	0.38	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.1
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.41
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.018	D
Polyphen		0.94	P
Vest4		0.64
MutPred		0.43		Gain of disorder (P = 0.0135)
MVP		0.94
MPC		0.30
ClinPred		0.73	D
GERP RS		4.0
PromoterAI		0.075	Neutral
Varity_R		0.59
gMVP		0.84
Mutation Taster		=92/8	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: rs879173625; hg19: chr3-128598551;