16-89093708-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000537895.5(ACSF3):c.-130+5230C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 151,764 control chromosomes in the GnomAD database, including 26 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 (26 hom., cov: 33)
  • Exomes 𝑓: 0.0066 (0 hom.)
• Consequence: ACSF3 ENST00000537895.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.246

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=-0.77).
• BP6: Variant 16-89093708-C-T is Benign according to our data. Variant chr16-89093708-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1329720.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0115 (1740/151312) while in subpopulation AFR AF= 0.0351 (1457/41468). AF 95% confidence interval is 0.0336. There are 26 homozygotes in gnomad4. There are 891 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 25 AR gene

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+5230C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0114 AC: 1721 AN: 151210 Hom.: 25 Cov.: 33

Gnomad AFR AF: 0.0348

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00539

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0346

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000222

Gnomad OTH AF: 0.00917

GnomAD4 exome AF: 0.00664 AC: 3 AN: 452 Hom.: 0 AF XY: 0.00585 AC XY: 2 AN XY: 342

Gnomad4 AFR exome AF: 0.0833

Gnomad4 AMR 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: 0.00508

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0115 AC: 1740 AN: 151312 Hom.: 26 Cov.: 33 AF XY: 0.0121 AC XY: 891 AN XY: 73898

Gnomad4 AFR AF: 0.0351

Gnomad4 AMR AF: 0.00538

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0346

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000222

Gnomad4 OTH AF: 0.00907

Alfa AF: 0.00840 Hom.: 2

Bravo AF: 0.0121

Asia WGS AF: 0.0190 AC: 67 AN: 3456

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	8.1
Dann	Benign	0.88

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10163334; hg19: chr16-89160116;