3-128884004-A-G

Variant names:

• chr3-128884004-A-G
• rs789231
• NM_014049.5:c.151-649A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014049.5(ACAD9):​c.151-649A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 151,996 control chromosomes in the GnomAD database, including 13,564 homozygotes. 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: 𝑓 0.39 (13564 hom., cov: 32)
• Consequence: ACAD9 NM_014049.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134
• Publications: 5 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 Gene-Disease associations (from GenCC):

• acyl-CoA dehydrogenase 9 deficiency

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACAD9	NM_014049.5	c.151-649A>G		intron_variant	Intron 1 of 17	ENST00000308982.12	NP_054768.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACAD9	ENST00000308982.12	c.151-649A>G		intron_variant	Intron 1 of 17	1	NM_014049.5	ENSP00000312618.7

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59719 AN: 151878 Hom.: 13541 Cov.: 32

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.396

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.393 AC: 59792 AN: 151996 Hom.: 13564 Cov.: 32 AF XY: 0.388 AC XY: 28820 AN XY: 74288

African (AFR) AF: 0.618 AC: 25620 AN: 41440

American (AMR) AF: 0.380 AC: 5796 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1343 AN: 3466

East Asian (EAS) AF: 0.555 AC: 2858 AN: 5154

South Asian (SAS) AF: 0.271 AC: 1308 AN: 4822

European-Finnish (FIN) AF: 0.237 AC: 2505 AN: 10574

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19238 AN: 67960

Other (OTH) AF: 0.396 AC: 835 AN: 2110

Alfa AF: 0.242 Hom.: 861

Bravo AF: 0.417

Asia WGS AF: 0.387 AC: 1345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.3
DANN	Benign	0.81
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

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: rs789231; hg19: chr3-128602847;