3-128879367-C-A

Variant names:

• chr3-128879367-C-A
• rs531128921
• ENST00000692129.1:n.67G>T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NR_186174.1(ACAD9-DT):​n.70G>T 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 0.00116 in 504,328 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0030 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00035 (1 hom.)
• Consequence: ACAD9-DT NR_186174.1 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.31

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 3-128879367-C-A is Benign according to our data. Variant chr3-128879367-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1193289.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACAD9-DT	NR_186174.1	n.70G>T		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACAD9-DT	ENST00000692129.1	n.67G>T		non_coding_transcript_exon_variant	Exon 1 of 3
ACAD9-DT	ENST00000692357.2	n.109G>T		non_coding_transcript_exon_variant	Exon 1 of 1
ACAD9	ENST00000681367.1	c.-325C>A		upstream_gene_variant				ENSP00000505309.1

Frequencies

GnomAD3 genomes AF: 0.00302 AC: 460 AN: 152252 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.0106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000981

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.000352 AC: 124 AN: 351958 Hom.: 1 AF XY: 0.000283 AC XY: 52 AN XY: 184062

Gnomad4 AFR exome AF: 0.00931

Gnomad4 AMR exome AF: 0.000813

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000248

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000956

Gnomad4 OTH exome AF: 0.000534

GnomAD4 genome AF: 0.00304 AC: 463 AN: 152370 Hom.: 2 Cov.: 33 AF XY: 0.00235 AC XY: 175 AN XY: 74518

Gnomad4 AFR AF: 0.0106

Gnomad4 AMR AF: 0.000980

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00284

Bravo AF: 0.00331

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 28, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.4
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs531128921; hg19: chr3-128598210;