rs748382994

chr16-89145305-C-Gchr16-89145305-C-T

Variant summary

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

The NM_001243279.3(ACSF3):c.1405C>G(p.Arg469Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R469Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ACSF3 NM_001243279.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41

Genes affected

ACSF3 (HGNC:27288): (acyl-CoA synthetase family member 3) This gene encodes a member of the acyl-CoA synthetase family of enzymes that activate fatty acids by catalyzing the formation of a thioester linkage between fatty acids and coenzyme A. The encoded protein is localized to mitochondria, has high specificity for malonate and methylmalonate and possesses malonyl-CoA synthetase activity. Mutations in this gene are a cause of combined malonic and methylmalonic aciduria. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Sep 2013]

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	UniProt
ACSF3	NM_001243279.3	c.1405C>G	p.Arg469Gly	missense_variant	9/11	ENST00000614302.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSF3	ENST00000614302.5	c.1405C>G	p.Arg469Gly	missense_variant	9/11	5	NM_001243279.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.12	T;T;T;T;.
Eigen	Benign	-0.032
Eigen_PC	Benign	0.026
FATHMM_MKL	Benign	0.75	D
M_CAP	Benign	0.052	D
MetaRNN	Uncertain	0.63	D;D;D;D;D
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.8	L;L;L;.;.
MutationTaster	Benign	0.96	N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.6	D;.;D;D;D
REVEL	Benign	0.24
Sift	Uncertain	0.010	D;.;D;D;D
Sift4G	Uncertain	0.0050	D;D;D;D;D
Polyphen		0.28	B;B;B;.;.
Vest4		0.63
MutPred		0.75		Loss of MoRF binding (P = 0.0133);Loss of MoRF binding (P = 0.0133);Loss of MoRF binding (P = 0.0133);.;.;
MVP		0.46
MPC		0.18
ClinPred		0.94	D
GERP RS		2.5
Varity_R		0.41
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs748382994; hg19: chr16-89211713;