12-120737052-C-G

Position:

• chr12-120737052-C-G

Variant summary

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

The NM_000017.4(ACADS):​c.277C>G​(p.Leu93Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ACADS NM_000017.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.98

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]

ACADS (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACADS	NM_000017.4	c.277C>G	p.Leu93Val	missense_variant	3/10	ENST00000242592.9	NP_000008.1
ACADS	NM_001302554.2	c.277C>G	p.Leu93Val	missense_variant	3/10		NP_001289483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACADS	ENST00000242592.9	c.277C>G	p.Leu93Val	missense_variant	3/10	1	NM_000017.4	ENSP00000242592.4
ACADS	ENST00000411593.2	c.277C>G	p.Leu93Val	missense_variant	3/10	2		ENSP00000401045.2
ACADS	ENST00000539690.1	n.389C>G		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000423 AC: 1 AN: 236320 Hom.: 0 AF XY: 0.00000781 AC XY: 1 AN XY: 128020

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: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000938

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.91	D;D
Eigen	Benign	0.018
Eigen_PC	Benign	0.046
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.99	D;D
M_CAP	Benign	0.063	D
MetaRNN	Uncertain	0.74	D;D
MetaSVM	Pathogenic	1.2	D
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.7	D;D
REVEL	Uncertain	0.63
Sift	Benign	0.12	T;T
Sift4G	Benign	0.22	T;T
Polyphen		0.070	B;P
Vest4		0.65
MutPred		0.59		Gain of helix (P = 0.2059);Gain of helix (P = 0.2059);
MVP		0.96
MPC		0.32
ClinPred		0.69	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.56
gMVP		0.78

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: rs1358146160; hg19: chr12-121174855;