3-128879626-CGT-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_014049.5(ACAD9):c.-57_-56del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,585,160 control chromosomes in the GnomAD database, including 83,489 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (13536 hom., cov: 0)
  • Exomes 𝑓: 0.30 (69953 hom.)
• Consequence: ACAD9 NM_014049.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.290

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 3-128879626-CGT-C is Benign according to our data. Variant chr3-128879626-CGT-C is described in ClinVar as [Benign]. Clinvar id is 343189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACAD9	NM_014049.5	c.-57_-56del		5_prime_UTR_variant	1/18	ENST00000308982.12
ACAD9	NM_001410805.1	c.-332_-331del		5_prime_UTR_variant	1/17
ACAD9	NR_033426.2	n.16_17del		non_coding_transcript_exon_variant	1/18
ACAD9	XR_427367.4	n.16_17del		non_coding_transcript_exon_variant	1/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACAD9	ENST00000308982.12	c.-57_-56del		5_prime_UTR_variant	1/18	1	NM_014049.5	P1

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59660 AN: 151738 Hom.: 13513 Cov.: 0

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.396

GnomAD3 exomes AF: 0.333 AC: 82499 AN: 247442 Hom.: 15389 AF XY: 0.326 AC XY: 43880 AN XY: 134788

Gnomad AFR exome AF: 0.626

Gnomad AMR exome AF: 0.330

Gnomad ASJ exome AF: 0.390

Gnomad EAS exome AF: 0.581

Gnomad SAS exome AF: 0.265

Gnomad FIN exome AF: 0.244

Gnomad NFE exome AF: 0.286

Gnomad OTH exome AF: 0.319

GnomAD4 exome AF: 0.303 AC: 434806 AN: 1433306 Hom.: 69953 AF XY: 0.302 AC XY: 215648 AN XY: 714612

Gnomad4 AFR exome AF: 0.634

Gnomad4 AMR exome AF: 0.333

Gnomad4 ASJ exome AF: 0.394

Gnomad4 EAS exome AF: 0.566

Gnomad4 SAS exome AF: 0.268

Gnomad4 FIN exome AF: 0.243

Gnomad4 NFE exome AF: 0.285

Gnomad4 OTH exome AF: 0.327

GnomAD4 genome AF: 0.393 AC: 59733 AN: 151854 Hom.: 13536 Cov.: 0 AF XY: 0.388 AC XY: 28789 AN XY: 74258

Gnomad4 AFR AF: 0.620

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.553

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.396

Alfa AF: 0.233 Hom.: 778

Bravo AF: 0.417

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Acyl-CoA dehydrogenase 9 deficiency Benign:3

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs397874507; hg19: chr3-128598469;