Variant 16-89094016-C-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+20C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 160,124 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 29 hom., cov: 32)

Exomes 𝑓: 0.020 ( 17 hom. )

Consequence

ACSF3
NM_001243279.3 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.619

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=-0.78).

BP6

Variant 16-89094016-C-G is Benign according to our data. Variant chr16-89094016-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 379938.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSF3	NM_001243279.3 link	c.-194+20C>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+20C>G		intron_variant	Intron 1 of 10	5	NM_001243279.3	ENSP00000479130.1		Q4G176

Frequencies

GnomAD3 genomes

AF:

0.0124

AC:

1851

AN:

148716

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0364

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00594

Gnomad ASJ

AF:

0.0176

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0351

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000300

Gnomad OTH

AF:

0.00977

GnomAD3 exomes

AF:

0.0250

AC:

AN:

2196

Hom.:

AF XY:

0.0252

AC XY:

AN XY:

1506

show subpopulations

Gnomad AFR exome

AF:

0.250

Gnomad AMR exome

AF:

0.0299

Gnomad ASJ exome

AF:

0.0672

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0674

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00168

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0200

AC:

226

AN:

11302

Hom.:

Cov.:

AF XY:

0.0224

AC XY:

182

AN XY:

8136

show subpopulations

Gnomad4 AFR exome

AF:

0.0984

Gnomad4 AMR exome

AF:

0.0169

Gnomad4 ASJ exome

AF:

0.0442

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0996

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00165

Gnomad4 OTH exome

AF:

0.0152

GnomAD4 genome

AF:

0.0125

AC:

1865

AN:

148822

Hom.:

Cov.:

AF XY:

0.0131

AC XY:

952

AN XY:

72558

show subpopulations

Gnomad4 AFR

AF:

0.0366

Gnomad4 AMR

AF:

0.00593

Gnomad4 ASJ

AF:

0.0176

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0351

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000300

Gnomad4 OTH

AF:

0.00966

Alfa

AF:

0.000353

Hom.:

Asia WGS

AF:

0.0210

AC:

AN:

3040

ClinVar

Significance: Likely 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: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 29, 2018

GeneDx

Significance: Likely 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

-0.78

CADD

Benign

8.1

DANN

Benign

0.53

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