chr11-134253632-C-G

Variant names:

• chr11-134253632-C-G
• rs773403936
• NM_014384.3:c.32C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014384.3(ACAD8):​c.32C>G​(p.Ala11Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,431,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ACAD8 NM_014384.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.770

Genes affected

ACAD8 (HGNC:87): (acyl-CoA dehydrogenase family member 8) This gene encodes a member of the acyl-CoA dehydrogenase family of enzymes that catalyze the dehydrogenation of acyl-CoA derivatives in the metabolism of fatty acids or branch chained amino acids. The encoded protein is a mitochondrial enzyme that functions in catabolism of the branched-chain amino acid valine. Defects in this gene are the cause of isobutyryl-CoA dehydrogenase deficiency.[provided by RefSeq, Nov 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13006645).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACAD8	NM_014384.3	c.32C>G	p.Ala11Gly	missense_variant	Exon 1 of 11	ENST00000281182.9	NP_055199.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACAD8	ENST00000281182.9	c.32C>G	p.Ala11Gly	missense_variant	Exon 1 of 11	1	NM_014384.3	ENSP00000281182.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000534 AC: 1 AN: 187300 Hom.: 0 AF XY: 0.00000969 AC XY: 1 AN XY: 103248

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000381

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1431456 Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1 AN XY: 710166

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000241

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000850 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	6.7
DANN	Benign	0.88
DEOGEN2	Benign	0.32	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.31	T;T
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.13	T;T
MetaSVM	Uncertain	0.25	D
MutationAssessor	Benign	0.69	N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.44	N;N
REVEL	Benign	0.21
Sift	Benign	0.38	T;D
Sift4G	Benign	0.38	T;T
Polyphen		0.099	B;.
Vest4		0.23
MutPred		0.41		Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);
MVP		0.79
MPC		0.15
ClinPred		0.035	T
GERP RS		-1.6
Varity_R		0.034
gMVP		0.55

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: rs773403936; hg19: chr11-134123526;