16-89100533-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001243279.3(ACSF3):c.-20-129C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 892,160 control chromosomes in the GnomAD database, including 216,453 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (39703 hom., cov: 33)
  • Exomes 𝑓: 0.68 (176750 hom.)
• Consequence: ACSF3 NM_001243279.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.73

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 16-89100533-C-T is Benign according to our data. Variant chr16-89100533-C-T is described in ClinVar as [Benign]. Clinvar id is 1188936.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSF3	NM_001243279.3	c.-20-129C>T		intron_variant		ENST00000614302.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSF3	ENST00000614302.5	c.-20-129C>T		intron_variant		5	NM_001243279.3	P1

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108906 AN: 152018 Hom.: 39682 Cov.: 33

Gnomad AFR AF: 0.623

Gnomad AMI AF: 0.762

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.726

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.729

GnomAD4 exome AF: 0.685 AC: 506887 AN: 740024 Hom.: 176750 AF XY: 0.682 AC XY: 256652 AN XY: 376336

Gnomad4 AFR exome AF: 0.555

Gnomad4 AMR exome AF: 0.764

Gnomad4 ASJ exome AF: 0.680

Gnomad4 EAS exome AF: 0.462

Gnomad4 SAS exome AF: 0.510

Gnomad4 FIN exome AF: 0.761

Gnomad4 NFE exome AF: 0.716

Gnomad4 OTH exome AF: 0.681

GnomAD4 genome AF: 0.716 AC: 108969 AN: 152136 Hom.: 39703 Cov.: 33 AF XY: 0.711 AC XY: 52915 AN XY: 74382

Gnomad4 AFR AF: 0.622

Gnomad4 AMR AF: 0.782

Gnomad4 ASJ AF: 0.714

Gnomad4 EAS AF: 0.445

Gnomad4 SAS AF: 0.548

Gnomad4 FIN AF: 0.753

Gnomad4 NFE AF: 0.785

Gnomad4 OTH AF: 0.728

Alfa AF: 0.751 Hom.: 5374

Bravo AF: 0.717

Asia WGS AF: 0.546 AC: 1898 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Combined malonic and methylmalonic acidemia Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.093
Dann	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7195892; hg19: chr16-89166941;