rs7202996

Positions:

• chr16-89104162-G-A
• chr16-89104162-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001243279.3(ACSF3):​c.822+1403G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 152,158 control chromosomes in the GnomAD database, including 32,907 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.65 (32907 hom., cov: 34)
• Consequence: ACSF3 NM_001243279.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.851

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACSF3	NM_001243279.3	c.822+1403G>A		intron_variant		ENST00000614302.5	NP_001230208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSF3	ENST00000614302.5	c.822+1403G>A		intron_variant		5	NM_001243279.3	ENSP00000479130	P1

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98696 AN: 152040 Hom.: 32893 Cov.: 34

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.678

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

GnomAD4 genome AF: 0.649 AC: 98736 AN: 152158 Hom.: 32907 Cov.: 34 AF XY: 0.643 AC XY: 47784 AN XY: 74364

Gnomad4 AFR AF: 0.547

Gnomad4 AMR AF: 0.737

Gnomad4 ASJ AF: 0.709

Gnomad4 EAS AF: 0.310

Gnomad4 SAS AF: 0.499

Gnomad4 FIN AF: 0.632

Gnomad4 NFE AF: 0.725

Gnomad4 OTH AF: 0.676

Alfa AF: 0.687 Hom.: 4520

Bravo AF: 0.654

Asia WGS AF: 0.458 AC: 1593 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs7202996; hg19: chr16-89170570;