3-128879626-CGT-C

Variant names:

• chr3-128879626-CGT-C
• rs397874507
• NM_014049.5:c.-57_-56delGT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_014049.5(ACAD9):​c.-57_-56delGT 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]

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ACAD9	NM_014049.5	c.-57_-56delGT		5_prime_UTR_variant	Exon 1 of 18	ENST00000308982.12	NP_054768.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACAD9	ENST00000308982	c.-57_-56delGT		5_prime_UTR_variant	Exon 1 of 18	1	NM_014049.5	ENSP00000312618.7

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

GnomAD2 exomes AF: 0.333 AC: 82499 AN: 247442 AF XY: 0.326

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 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 AC: 20816 AN: 32836

Gnomad4 AMR exome AF: 0.333 AC: 14890 AN: 44670

Gnomad4 ASJ exome AF: 0.394 AC: 10247 AN: 25976

Gnomad4 EAS exome AF: 0.566 AC: 22389 AN: 39538

Gnomad4 SAS exome AF: 0.268 AC: 22923 AN: 85632

Gnomad4 FIN exome AF: 0.243 AC: 12750 AN: 52482

Gnomad4 NFE exome AF: 0.285 AC: 309971 AN: 1088714

Gnomad4 Remaining exome AF: 0.327 AC: 19402 AN: 59336

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 AC: 0.620115 AN: 0.620115

Gnomad4 AMR AF: 0.379 AC: 0.379353 AN: 0.379353

Gnomad4 ASJ AF: 0.386 AC: 0.386036 AN: 0.386036

Gnomad4 EAS AF: 0.553 AC: 0.553092 AN: 0.553092

Gnomad4 SAS AF: 0.270 AC: 0.270461 AN: 0.270461

Gnomad4 FIN AF: 0.236 AC: 0.23635 AN: 0.23635

Gnomad4 NFE AF: 0.283 AC: 0.282788 AN: 0.282788

Gnomad4 OTH AF: 0.396 AC: 0.395735 AN: 0.395735

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

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:1

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Name	Calibrated prediction	Score	Prediction
Mutation Taster		=299/1	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

Publications

LitVar

Other links and lift over

dbSNP: rs397874507; hg19: chr3-128598469; COSMIC: COSV58306364; COSMIC: COSV58306364;