chr12-120739440-C-G

Position:

• chr12-120739440-C-G

Variant summary

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

The NM_000017.4(ACADS):​c.1231C>G​(p.Arg411Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: ACADS NM_000017.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.87

Genes affected

ACADS (HGNC:90): (acyl-CoA dehydrogenase short chain) This gene encodes a tetrameric mitochondrial flavoprotein, which is a member of the acyl-CoA dehydrogenase family. This enzyme catalyzes the initial step of the mitochondrial fatty acid beta-oxidation pathway. Mutations in this gene have been associated with short-chain acyl-CoA dehydrogenase (SCAD) deficiency. Alternative splicing results in two variants which encode different isoforms. [provided by RefSeq, Oct 2014]

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=0.23375872).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACADS	NM_000017.4	c.1231C>G	p.Arg411Gly	missense_variant	10/10	ENST00000242592.9	NP_000008.1
ACADS	NM_001302554.2	c.1219C>G	p.Arg407Gly	missense_variant	10/10		NP_001289483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACADS	ENST00000242592.9	c.1231C>G	p.Arg411Gly	missense_variant	10/10	1	NM_000017.4	ENSP00000242592.4
ACADS	ENST00000411593.2	c.1219C>G	p.Arg407Gly	missense_variant	10/10	2		ENSP00000401045.2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152174 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152174 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74348

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

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: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.057
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.59	T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Uncertain	0.32	D
MutationAssessor	Benign	-0.42	N;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	1.2	N;N
REVEL	Uncertain	0.47
Sift	Benign	0.056	T;T
Sift4G	Benign	0.20	T;T
Polyphen		0.0020	B;.
Vest4		0.51
MutPred		0.37		Gain of relative solvent accessibility (P = 0.0275);.;
MVP		0.97
MPC		0.51
ClinPred		0.97	D
GERP RS		3.9
Varity_R		0.66
gMVP		0.60

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: rs369416846; hg19: chr12-121177243;