rs143793502

Positions:

• chr16-89112123-C-A
• chr16-89112123-C-T

Variant summary

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

The NM_001243279.3(ACSF3):​c.854C>A​(p.Pro285Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000182 in 1,096,398 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P285L) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: ACSF3 NM_001243279.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.17

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	Protein	UniProt
ACSF3	NM_001243279.3	c.854C>A	p.Pro285Gln	missense_variant	5/11	ENST00000614302.5	NP_001230208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSF3	ENST00000614302.5	c.854C>A	p.Pro285Gln	missense_variant	5/11	5	NM_001243279.3	ENSP00000479130.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.00000857 AC: 2 AN: 233436 Hom.: 0 AF XY: 0.0000158 AC XY: 2 AN XY: 126676

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: 0.0000187

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1096398 Hom.: 0 Cov.: 41 AF XY: 0.00000373 AC XY: 2 AN XY: 536312

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: 0.00000225

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	22
DANN	Benign	0.89
DEOGEN2	Benign	0.30	.;T;T;.;T;T;.;T
Eigen	Benign	-0.087
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D;.;D;D;.;D;D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.71	D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Benign	1.2	.;L;L;.;L;.;.;.
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-4.8	D;D;.;D;D;D;D;D
REVEL	Benign	0.22
Sift	Benign	0.14	T;T;.;T;T;T;T;T
Sift4G	Benign	0.14	T;T;T;T;T;T;T;T
Polyphen		0.47	.;P;P;.;P;.;.;.
Vest4		0.65, 0.73
MutPred		0.53		.;Loss of sheet (P = 0.1501);Loss of sheet (P = 0.1501);.;Loss of sheet (P = 0.1501);.;.;.;
MVP		0.55
MPC		0.25
ClinPred		0.93	D
GERP RS		4.5
Varity_R		0.13
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs143793502; hg19: chr16-89178531;