Variant 16-89094044-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001243279.3(ACSF3):c.-194+48A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 150,950 control chromosomes in the GnomAD database, including 36,097 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 35604 hom., cov: 30)

Exomes 𝑓: 0.66 ( 493 hom. )

Consequence

ACSF3
NM_001243279.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.63

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 16-89094044-A-G is Benign according to our data. Variant chr16-89094044-A-G is described in ClinVar as [Benign]. Clinvar id is 1177766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSF3	NM_001243279.3 link	c.-194+48A>G		intron_variant	Intron 1 of 10	ENST00000614302.5	NP_001230208.1	Q4G176

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSF3	ENST00000614302.5 link	c.-194+48A>G		intron_variant	Intron 1 of 10	5	NM_001243279.3	ENSP00000479130.1		Q4G176

Frequencies

GnomAD3 genomes

AF:

0.685

AC:

101757

AN:

148598

Hom.:

35585

Cov.:

show subpopulations

Gnomad AFR

AF:

0.531

Gnomad AMI

AF:

0.614

Gnomad AMR

AF:

0.753

Gnomad ASJ

AF:

0.630

Gnomad EAS

AF:

0.785

Gnomad SAS

AF:

0.734

Gnomad FIN

AF:

0.717

Gnomad MID

AF:

0.713

Gnomad NFE

AF:

0.751

Gnomad OTH

AF:

0.698

GnomAD4 exome

AF:

0.659

AC:

1479

AN:

2244

Hom.:

493

Cov.:

AF XY:

0.654

AC XY:

1104

AN XY:

1688

show subpopulations

Gnomad4 AFR exome

AF:

0.500

Gnomad4 AMR exome

AF:

0.850

Gnomad4 ASJ exome

AF:

0.438

Gnomad4 EAS exome

AF:

0.745

Gnomad4 SAS exome

AF:

0.353

Gnomad4 FIN exome

AF:

0.708

Gnomad4 NFE exome

AF:

0.676

Gnomad4 OTH exome

AF:

0.604

GnomAD4 genome

AF:

0.685

AC:

101806

AN:

148706

Hom.:

35604

Cov.:

AF XY:

0.685

AC XY:

49715

AN XY:

72536

show subpopulations

Gnomad4 AFR

AF:

0.530

Gnomad4 AMR

AF:

0.754

Gnomad4 ASJ

AF:

0.630

Gnomad4 EAS

AF:

0.784

Gnomad4 SAS

AF:

0.736

Gnomad4 FIN

AF:

0.717

Gnomad4 NFE

AF:

0.751

Gnomad4 OTH

AF:

0.702

Alfa

AF:

0.706

Hom.:

4777

Asia WGS

AF:

0.730

AC:

2252

AN:

3086

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.3

DANN

Benign

0.46

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over