chr12-120725907-C-G

Variant names:

• chr12-120725907-C-G
• rs777704501
• NM_000017.4:c.22C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000017.4(ACADS):​c.22C>G​(p.Arg8Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000712 in 1,404,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 7.1e-7 (0 hom.)
• Consequence: ACADS NM_000017.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.513

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29945433).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACADS	NM_000017.4	c.22C>G	p.Arg8Gly	missense_variant	Exon 1 of 10	ENST00000242592.9	NP_000008.1
ACADS	NM_001302554.2	c.22C>G	p.Arg8Gly	missense_variant	Exon 1 of 10		NP_001289483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACADS	ENST00000242592.9	c.22C>G	p.Arg8Gly	missense_variant	Exon 1 of 10	1	NM_000017.4	ENSP00000242592.4
ACADS	ENST00000411593.2	c.22C>G	p.Arg8Gly	missense_variant	Exon 1 of 10	2		ENSP00000401045.2
ACADS	ENST00000539690.1	n.134C>G		non_coding_transcript_exon_variant	Exon 1 of 3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.12e-7 AC: 1 AN: 1404256 Hom.: 0 Cov.: 31 AF XY: 0.00000144 AC XY: 1 AN XY: 695902

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.15e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000902 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.095	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	19
DANN	Benign	0.92
DEOGEN2	Benign	0.40	T;T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.77	T;T
M_CAP	Pathogenic	0.48	D
MetaRNN	Benign	0.30	T;T
MetaSVM	Uncertain	0.22	D
MutationAssessor	Benign	0.0	N;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.1	N;N
REVEL	Uncertain	0.40
Sift	Uncertain	0.014	D;D
Sift4G	Benign	0.12	T;T
Polyphen		0.0010	B;B
Vest4		0.20
MutPred		0.49		Loss of MoRF binding (P = 2e-04);Loss of MoRF binding (P = 2e-04);
MVP		0.89
MPC		0.25
ClinPred		0.28	T
GERP RS		1.1
Varity_R		0.20
gMVP		0.59

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: rs777704501; hg19: chr12-121163710;