Variant 16-89098586-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001243279.3(ACSF3):c.-193-5G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00519 in 450,868 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0048 ( 6 hom., cov: 34)

Exomes 𝑓: 0.0054 ( 9 hom. )

Consequence

ACSF3
NM_001243279.3 splice_region, intron

Scores

Splicing: ADA: 0.00009940

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.181

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 16-89098586-G-C is Benign according to our data. Variant chr16-89098586-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 380080.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00476 (726/152372) while in subpopulation AMR AF= 0.00757 (116/15314). AF 95% confidence interval is 0.00646. There are 6 homozygotes in gnomad4. There are 364 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSF3	NM_001243279.3 link	c.-193-5G>C		splice_region_variant, 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.-193-5G>C		splice_region_variant, intron_variant	Intron 1 of 10	5	NM_001243279.3	ENSP00000479130.1		Q4G176

Frequencies

GnomAD3 genomes

AF:

0.00477

AC:

726

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00758

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00442

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00676

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00540

AC:

696

AN:

128956

Hom.:

AF XY:

0.00512

AC XY:

361

AN XY:

70462

show subpopulations

Gnomad AFR exome

AF:

0.00164

Gnomad AMR exome

AF:

0.00645

Gnomad ASJ exome

AF:

0.0126

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000135

Gnomad FIN exome

AF:

0.00510

Gnomad NFE exome

AF:

0.00783

Gnomad OTH exome

AF:

0.00452

GnomAD4 exome

AF:

0.00541

AC:

1615

AN:

298496

Hom.:

Cov.:

AF XY:

0.00520

AC XY:

882

AN XY:

169688

show subpopulations

Gnomad4 AFR exome

AF:

0.00141

Gnomad4 AMR exome

AF:

0.00650

Gnomad4 ASJ exome

AF:

0.0119

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000252

Gnomad4 FIN exome

AF:

0.00675

Gnomad4 NFE exome

AF:

0.00720

Gnomad4 OTH exome

AF:

0.00531

GnomAD4 genome

AF:

0.00476

AC:

726

AN:

152372

Hom.:

Cov.:

AF XY:

0.00488

AC XY:

364

AN XY:

74520

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.00757

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00442

Gnomad4 NFE

AF:

0.00676

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00560

Hom.:

Bravo

AF:

0.00505

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 13, 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

-0.83

CADD

Benign

1.0

DANN

Benign

0.42

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000099

dbscSNV1_RF

Benign

0.044

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