16-89093750-G-C

Variant summary

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

The ENST00000537895.5(ACSF3):c.-130+5272G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 151,926 control chromosomes in the GnomAD database, including 36,819 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.69 (36521 hom., cov: 31)
  • Exomes 𝑓: 0.75 (298 hom.)
• Consequence: ACSF3 ENST00000537895.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.242

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=-0.83).
• BP6: Variant 16-89093750-G-C is Benign according to our data. Variant chr16-89093750-G-C is described in ClinVar as [Benign]. Clinvar id is 1266611.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSF3	ENST00000537895.5	c.-130+5272G>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.688 AC: 103760 AN: 150762 Hom.: 36502 Cov.: 31

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.817

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.713

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.701

GnomAD4 exome AF: 0.748 AC: 790 AN: 1056 Hom.: 298 AF XY: 0.742 AC XY: 540 AN XY: 728

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.792

Gnomad4 SAS exome AF: 0.580

Gnomad4 FIN exome AF: 0.833

Gnomad4 NFE exome AF: 0.759

Gnomad4 OTH exome AF: 0.800

GnomAD4 genome AF: 0.688 AC: 103809 AN: 150870 Hom.: 36521 Cov.: 31 AF XY: 0.690 AC XY: 50855 AN XY: 73702

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.756

Gnomad4 ASJ AF: 0.630

Gnomad4 EAS AF: 0.816

Gnomad4 SAS AF: 0.742

Gnomad4 FIN AF: 0.736

Gnomad4 NFE AF: 0.753

Gnomad4 OTH AF: 0.705

Alfa AF: 0.710 Hom.: 4732

Bravo AF: 0.685

Asia WGS AF: 0.756 AC: 2493 AN: 3296

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	-0.83
Cadd	Benign	4.0
Dann	Benign	0.25

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs76688594; hg19: chr16-89160158;