16-89133188-C-G

Position:

• chr16-89133188-C-G

Variant summary

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

The NM_001243279.3(ACSF3):​c.1292C>G​(p.Ser431Cys) 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: ACSF3 NM_001243279.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.83

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]

ACSF3 (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
ACSF3	NM_001243279.3	c.1292C>G	p.Ser431Cys	missense_variant	8/11	ENST00000614302.5	NP_001230208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSF3	ENST00000614302.5	c.1292C>G	p.Ser431Cys	missense_variant	8/11	5	NM_001243279.3	ENSP00000479130.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.30	T;T;.;T;T;.
Eigen	Uncertain	0.35
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.94	.;D;D;.;D;D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.68	D;D;D;D;D;D
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.1	M;M;.;M;.;.
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.6	D;.;D;D;D;D
REVEL	Benign	0.28
Sift	Uncertain	0.0080	D;.;D;D;D;D
Sift4G	Uncertain	0.015	D;D;D;D;D;D
Polyphen		0.99	D;D;.;D;.;.
Vest4		0.53
MutPred		0.67		Gain of catalytic residue at P430 (P = 0.0086);Gain of catalytic residue at P430 (P = 0.0086);.;Gain of catalytic residue at P430 (P = 0.0086);.;.;
MVP		0.52
MPC		0.29
ClinPred		0.89	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.31
gMVP		0.81

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: rs1057520194; hg19: chr16-89199596;