16-89094044-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001243279.3(ACSF3):c.-194+48A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 150,950 control chromosomes in the GnomAD database, including 36,097 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.68 (35604 hom., cov: 30)
  • Exomes 𝑓: 0.66 (493 hom.)
• Consequence: ACSF3 NM_001243279.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.63

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 16-89094044-A-G is Benign according to our data. Variant chr16-89094044-A-G is described in ClinVar as [Benign]. Clinvar id is 1177766.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSF3	NM_001243279.3	c.-194+48A>G		intron_variant		ENST00000614302.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSF3	ENST00000614302.5	c.-194+48A>G		intron_variant		5	NM_001243279.3	P1

Frequencies

GnomAD3 genomes AF: 0.685 AC: 101757 AN: 148598 Hom.: 35585 Cov.: 30

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.785

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.713

Gnomad NFE AF: 0.751

Gnomad OTH AF: 0.698

GnomAD4 exome AF: 0.659 AC: 1479 AN: 2244 Hom.: 493 Cov.: 0 AF XY: 0.654 AC XY: 1104 AN XY: 1688

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.850

Gnomad4 ASJ exome AF: 0.438

Gnomad4 EAS exome AF: 0.745

Gnomad4 SAS exome AF: 0.353

Gnomad4 FIN exome AF: 0.708

Gnomad4 NFE exome AF: 0.676

Gnomad4 OTH exome AF: 0.604

GnomAD4 genome AF: 0.685 AC: 101806 AN: 148706 Hom.: 35604 Cov.: 30 AF XY: 0.685 AC XY: 49715 AN XY: 72536

Gnomad4 AFR AF: 0.530

Gnomad4 AMR AF: 0.754

Gnomad4 ASJ AF: 0.630

Gnomad4 EAS AF: 0.784

Gnomad4 SAS AF: 0.736

Gnomad4 FIN AF: 0.717

Gnomad4 NFE AF: 0.751

Gnomad4 OTH AF: 0.702

Alfa AF: 0.706 Hom.: 4777

Asia WGS AF: 0.730 AC: 2252 AN: 3086

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	6.3
Dann	Benign	0.46

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: rs9938075; hg19: chr16-89160452;