3-128879702-G-T

Variant names:

• chr3-128879702-G-T
• rs863223872
• NM_014049.5:c.11G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_014049.5(ACAD9):​c.11G>T​(p.Cys4Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACAD9 NM_014049.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.06

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16834664).
• BP6: Variant 3-128879702-G-T is Benign according to our data. Variant chr3-128879702-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 213994.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACAD9	NM_014049.5	c.11G>T	p.Cys4Phe	missense_variant	Exon 1 of 18	ENST00000308982.12	NP_054768.2
ACAD9	NM_001410805.1	c.-265G>T		5_prime_UTR_variant	Exon 1 of 17		NP_001397734.1
ACAD9	NR_033426.2	n.83G>T		non_coding_transcript_exon_variant	Exon 1 of 18
ACAD9	XR_427367.4	n.83G>T		non_coding_transcript_exon_variant	Exon 1 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACAD9	ENST00000308982.12	c.11G>T	p.Cys4Phe	missense_variant	Exon 1 of 18	1	NM_014049.5	ENSP00000312618.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 03, 2012

GeneDx

Significance: Likely 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
AlphaMissense	Benign	0.065
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	4.6
DANN	Benign	0.97
DEOGEN2	Benign	0.20	T;.
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.52	T;T
M_CAP	Pathogenic	0.34	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Uncertain	-0.0044	T
MutationAssessor	Uncertain	2.6	M;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.55	N;N
REVEL	Benign	0.26
Sift	Uncertain	0.023	D;D
Sift4G	Benign	0.11	T;T
Polyphen		0.028	B;.
Vest4		0.22
MutPred		0.32		Loss of catalytic residue at C4 (P = 0.0537);Loss of catalytic residue at C4 (P = 0.0537);
MVP		0.80
MPC		0.35
ClinPred		0.056	T
GERP RS		-0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.11
gMVP		0.51

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: rs863223872; hg19: chr3-128598545;