16-89100399-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.-20-263A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 152,236 control chromosomes in the GnomAD database, including 39,700 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.72 (39700 hom., cov: 34)
• Consequence: ACSF3 NM_001243279.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0310

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 16-89100399-A-G is Benign according to our data. Variant chr16-89100399-A-G is described in ClinVar as [Benign]. Clinvar id is 1271277.Status of the report is criteria_provided_single_submitter, 1 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.-20-263A>G		intron_variant		ENST00000614302.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSF3	ENST00000614302.5	c.-20-263A>G		intron_variant		5	NM_001243279.3	P1

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108934 AN: 152116 Hom.: 39679 Cov.: 34

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.762

Gnomad AMR AF: 0.781

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.728

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.716 AC: 108997 AN: 152236 Hom.: 39700 Cov.: 34 AF XY: 0.711 AC XY: 52927 AN XY: 74434

Gnomad4 AFR AF: 0.622

Gnomad4 AMR AF: 0.781

Gnomad4 ASJ AF: 0.714

Gnomad4 EAS AF: 0.444

Gnomad4 SAS AF: 0.548

Gnomad4 FIN AF: 0.753

Gnomad4 NFE AF: 0.785

Gnomad4 OTH AF: 0.727

Alfa AF: 0.751 Hom.: 5373

Bravo AF: 0.716

Asia WGS AF: 0.546 AC: 1900 AN: 3478

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

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.9
Dann	Benign	0.54

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: rs12449019; hg19: chr16-89166807;