16-89100424-G-A

Variant names:

• chr16-89100424-G-A
• rs12445614
• NM_001243279.3:c.-20-238G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001243279.3(ACSF3):​c.-20-238G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 152,210 control chromosomes in the GnomAD database, including 42,463 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.74 (42463 hom., cov: 34)
• Consequence: ACSF3 NM_001243279.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.08
• Publications: 4 publications found

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]

ACSF3 Gene-Disease associations (from GenCC):

• combined malonic and methylmalonic acidemia

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 16-89100424-G-A is Benign according to our data. Variant chr16-89100424-G-A is described in ClinVar as Benign. ClinVar VariationId is 1269527.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001243279.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSF3	NM_001243279.3	MANE Select	c.-20-238G>A		intron	N/A	NP_001230208.1	Q4G176
	ACSF3	NM_001127214.4		c.-20-238G>A		intron	N/A	NP_001120686.1	Q4G176
	ACSF3	NM_174917.5		c.-20-238G>A		intron	N/A	NP_777577.2	Q4G176

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSF3	ENST00000614302.5	TSL:5 MANE Select	c.-20-238G>A		intron	N/A	ENSP00000479130.1	Q4G176
	ACSF3	ENST00000378345.8	TSL:1	c.-129-2180G>A		intron	N/A	ENSP00000367596.4	F5H5A1
	ACSF3	ENST00000871968.1		c.-20-238G>A		intron	N/A	ENSP00000542027.1

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112814 AN: 152090 Hom.: 42445 Cov.: 34

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.762

Gnomad AMR AF: 0.791

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.875

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.799

Gnomad OTH AF: 0.756

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

GnomAD4 genome AF: 0.742 AC: 112873 AN: 152210 Hom.: 42463 Cov.: 34 AF XY: 0.743 AC XY: 55272 AN XY: 74424

African (AFR) AF: 0.629 AC: 26115 AN: 41508

American (AMR) AF: 0.791 AC: 12103 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 2562 AN: 3470

East Asian (EAS) AF: 0.586 AC: 3041 AN: 5186

South Asian (SAS) AF: 0.608 AC: 2935 AN: 4830

European-Finnish (FIN) AF: 0.875 AC: 9277 AN: 10600

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.799 AC: 54337 AN: 68000

Other (OTH) AF: 0.755 AC: 1594 AN: 2112

Alfa AF: 0.771 Hom.: 5671

Bravo AF: 0.734

Asia WGS AF: 0.637 AC: 2216 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.18
DANN	Benign	0.57
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12445614; hg19: chr16-89166832;