chr12-120738181-T-A

Variant names:

• chr12-120738181-T-A
• rs555404
• NM_000017.4:c.625-99T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000017.4(ACADS):​c.625-99T>A variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACADS NM_000017.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.88
• Publications: 25 publications found

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 Gene-Disease associations (from GenCC):

• short chain acyl-CoA dehydrogenase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Orphanet, ClinGen

ENSG00000255946 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07158196).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000017.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACADS	NM_000017.4	MANE Select	c.625-99T>A		intron	N/A	NP_000008.1
	ACADS	NM_001302554.2		c.605T>A	p.Leu202Gln	missense	Exon 5 of 10	NP_001289483.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACADS	ENST00000242592.9	TSL:1 MANE Select	c.625-99T>A		intron	N/A	ENSP00000242592.4
	ACADS	ENST00000411593.2	TSL:2	c.605T>A	p.Leu202Gln	missense	Exon 5 of 10	ENSP00000401045.2
	ENSG00000255946	ENST00000724268.1		n.305-7893A>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 84

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	0.17
DANN	Benign	0.66
DEOGEN2	Benign	0.22	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.072	T
MetaSVM	Uncertain	0.034	D
PhyloP100		-2.9
PROVEAN	Benign	2.0	N
REVEL	Benign	0.22
Sift	Benign	0.28	T
Sift4G	Benign	0.38	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.42		Gain of solvent accessibility (P = 0.0273)
MVP		0.37
ClinPred		0.054	T
GERP RS		-0.70
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs555404; hg19: chr12-121175984;