16-89093875-C-G

Variant names:

• chr16-89093875-C-G
• rs562092702
• NM_001243279.3:c.-315C>G

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.-315C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00989 in 317,374 control chromosomes in the GnomAD database, including 92 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (84 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (8 hom.)
• Consequence: ACSF3 NM_001243279.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.542
• Publications: 0 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=-0.76).
• BP6: Variant 16-89093875-C-G is Benign according to our data. Variant chr16-89093875-C-G is described in ClinVar as Benign. ClinVar VariationId is 1296438.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0638 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.-315C>G		5_prime_UTR	Exon 1 of 11	NP_001230208.1	Q4G176
	ACSF3	NM_001127214.4		c.-142C>G		5_prime_UTR	Exon 1 of 10	NP_001120686.1	Q4G176
	ACSF3	NM_174917.5		c.-311C>G		5_prime_UTR	Exon 1 of 11	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.-315C>G		5_prime_UTR	Exon 1 of 11	ENSP00000479130.1	Q4G176
	ACSF3	ENST00000871968.1		c.-315C>G		5_prime_UTR	Exon 1 of 12	ENSP00000542027.1
	ACSF3	ENST00000966008.1		c.-315C>G		5_prime_UTR	Exon 1 of 12	ENSP00000636067.1

Frequencies

GnomAD3 genomes AF: 0.0191 AC: 2858 AN: 150008 Hom.: 85 Cov.: 32

Gnomad AFR AF: 0.0661

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00563

Gnomad ASJ AF: 0.000580

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000238

Gnomad OTH AF: 0.0146

GnomAD2 exomes AF: 0.00131 AC: 92 AN: 70104 AF XY: 0.000932

Gnomad AFR exome AF: 0.0630

Gnomad AMR exome AF: 0.00205

Gnomad ASJ exome AF: 0.000801

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000774

Gnomad OTH exome AF: 0.00198

GnomAD4 exome AF: 0.00167 AC: 279 AN: 167258 Hom.: 8 Cov.: 0 AF XY: 0.00107 AC XY: 110 AN XY: 103024

African (AFR) AF: 0.0550 AC: 185 AN: 3362

American (AMR) AF: 0.00216 AC: 33 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000696 AC: 5 AN: 7182

East Asian (EAS) AF: 0.00 AC: 0 AN: 1186

South Asian (SAS) AF: 0.000198 AC: 8 AN: 40454

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7518

Middle Eastern (MID) AF: 0.00305 AC: 2 AN: 656

European-Non Finnish (NFE) AF: 0.000130 AC: 11 AN: 84704

Other (OTH) AF: 0.00507 AC: 35 AN: 6900

GnomAD4 genome AF: 0.0190 AC: 2859 AN: 150116 Hom.: 84 Cov.: 32 AF XY: 0.0180 AC XY: 1323 AN XY: 73302

African (AFR) AF: 0.0659 AC: 2723 AN: 41326

American (AMR) AF: 0.00563 AC: 85 AN: 15106

Ashkenazi Jewish (ASJ) AF: 0.000580 AC: 2 AN: 3448

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9752

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000238 AC: 16 AN: 67222

Other (OTH) AF: 0.0144 AC: 30 AN: 2080

Alfa AF: 0.0150 Hom.: 6

Bravo AF: 0.0212

Asia WGS AF: 0.00318 AC: 10 AN: 3154

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	-0.76
CADD	Benign	3.2
DANN	Benign	0.72
PhyloP100		-0.54
PromoterAI		-0.10	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	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: rs562092702; hg19: chr16-89160283;