16-89094053-G-A

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+57G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 150,808 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (22 hom., cov: 32)
  • Exomes 𝑓: 0.020 (2 hom.)
• Consequence: ACSF3 NM_001243279.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.13

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=-0.88).
• BP6: Variant 16-89094053-G-A is Benign according to our data. Variant chr16-89094053-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1329765.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSF3	NM_001243279.3	c.-194+57G>A		intron_variant		ENST00000614302.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSF3	ENST00000614302.5	c.-194+57G>A		intron_variant		5	NM_001243279.3	P1

Frequencies

GnomAD3 genomes AF: 0.0110 AC: 1646 AN: 149650 Hom.: 21 Cov.: 32

Gnomad AFR AF: 0.0333

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00525

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0342

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000209

Gnomad OTH AF: 0.00870

GnomAD4 exome AF: 0.0200 AC: 21 AN: 1050 Hom.: 2 AF XY: 0.0231 AC XY: 18 AN XY: 780

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: 0.432

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00225

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0111 AC: 1659 AN: 149758 Hom.: 22 Cov.: 32 AF XY: 0.0115 AC XY: 841 AN XY: 73058

Gnomad4 AFR AF: 0.0335

Gnomad4 AMR AF: 0.00524

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0343

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000209

Gnomad4 OTH AF: 0.00860

Alfa AF: 0.00238 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 24, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	5.7
Dann	Benign	0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs552196056; hg19: chr16-89160461;