rs7202996

Variant names:

• chr16-89104162-G-A
• rs7202996
• NM_001243279.3:c.822+1403G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ACSF3	NM_001243279.3	c.822+1403G>A		intron_variant	Intron 4 of 10	ENST00000614302.5	NP_001230208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSF3	ENST00000614302.5	c.822+1403G>A		intron_variant	Intron 4 of 10	5	NM_001243279.3	ENSP00000479130.1

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

African (AFR) AF: 0.547 AC: 22705 AN: 41478

American (AMR) AF: 0.737 AC: 11269 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.709 AC: 2461 AN: 3472

East Asian (EAS) AF: 0.310 AC: 1609 AN: 5184

South Asian (SAS) AF: 0.499 AC: 2408 AN: 4824

European-Finnish (FIN) AF: 0.632 AC: 6691 AN: 10588

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.725 AC: 49315 AN: 68002

Other (OTH) AF: 0.676 AC: 1427 AN: 2110

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
PhyloP100		-0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs7202996; hg19: chr16-89170570;