3-128879524-T-G

Variant names:

• chr3-128879524-T-G
• rs183973851
• ENST00000692357.3:n.67A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000692357.3(ACAD9-DT):​n.67A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000013 in 770,618 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 34)
  • Exomes 𝑓: 0.0000013 (0 hom.)
• Consequence: ACAD9-DT ENST00000692357.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 4 publications found

Genes affected

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

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: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000692357.3. 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.-168T>G		upstream_gene	N/A	NP_054768.2
	ACAD9	NM_001410805.1		c.-443T>G		upstream_gene	N/A	NP_001397734.1	Q9H9W4
	ACAD9	NR_033426.2		n.-96T>G		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACAD9-DT	ENST00000692357.3		n.67A>C		non_coding_transcript_exon	Exon 1 of 1
	ACAD9	ENST00000308982.12	TSL:1 MANE Select	c.-168T>G		upstream_gene	N/A	ENSP00000312618.7	Q9H845
	ACAD9	ENST00000681367.1		c.-168T>G		upstream_gene	N/A	ENSP00000505309.1	A0A7P0T8U3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000130 AC: 1 AN: 770618 Hom.: 0 Cov.: 10 AF XY: 0.00000248 AC XY: 1 AN XY: 402942

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 20586

American (AMR) AF: 0.00 AC: 0 AN: 41588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19694

East Asian (EAS) AF: 0.00 AC: 0 AN: 36242

South Asian (SAS) AF: 0.00 AC: 0 AN: 68134

European-Finnish (FIN) AF: 0.0000270 AC: 1 AN: 37034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 507128

Other (OTH) AF: 0.00 AC: 0 AN: 37454

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.9
DANN	Benign	0.32
PhyloP100		-1.2
PromoterAI		0.25	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs183973851; hg19: chr3-128598367;