Variant 16-89100533-C-T 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.-20-129C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 892,160 control chromosomes in the GnomAD database, including 216,453 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 39703 hom., cov: 33)

Exomes 𝑓: 0.68 ( 176750 hom. )

Consequence

ACSF3
NM_001243279.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.73

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=-0.92).

BP6

Variant 16-89100533-C-T is Benign according to our data. Variant chr16-89100533-C-T is described in ClinVar as [Benign]. Clinvar id is 1188936.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSF3	NM_001243279.3 link	c.-20-129C>T		intron_variant	Intron 2 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.-20-129C>T		intron_variant	Intron 2 of 10	5	NM_001243279.3	ENSP00000479130.1		Q4G176

Frequencies

GnomAD3 genomes

AF:

0.716

AC:

108906

AN:

152018

Hom.:

39682

Cov.:

show subpopulations

Gnomad AFR

AF:

0.623

Gnomad AMI

AF:

0.762

Gnomad AMR

AF:

0.782

Gnomad ASJ

AF:

0.714

Gnomad EAS

AF:

0.445

Gnomad SAS

AF:

0.547

Gnomad FIN

AF:

0.753

Gnomad MID

AF:

0.726

Gnomad NFE

AF:

0.785

Gnomad OTH

AF:

0.729

GnomAD4 exome

AF:

0.685

AC:

506887

AN:

740024

Hom.:

176750

AF XY:

0.682

AC XY:

256652

AN XY:

376336

show subpopulations

Gnomad4 AFR exome

AF:

0.555

Gnomad4 AMR exome

AF:

0.764

Gnomad4 ASJ exome

AF:

0.680

Gnomad4 EAS exome

AF:

0.462

Gnomad4 SAS exome

AF:

0.510

Gnomad4 FIN exome

AF:

0.761

Gnomad4 NFE exome

AF:

0.716

Gnomad4 OTH exome

AF:

0.681

GnomAD4 genome

AF:

0.716

AC:

108969

AN:

152136

Hom.:

39703

Cov.:

AF XY:

0.711

AC XY:

52915

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.622

Gnomad4 AMR

AF:

0.782

Gnomad4 ASJ

AF:

0.714

Gnomad4 EAS

AF:

0.445

Gnomad4 SAS

AF:

0.548

Gnomad4 FIN

AF:

0.753

Gnomad4 NFE

AF:

0.785

Gnomad4 OTH

AF:

0.728

Alfa

AF:

0.751

Hom.:

5374

Bravo

AF:

0.717

Asia WGS

AF:

0.546

AC:

1898

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

- -

Combined malonic and methylmalonic acidemia

Benign:1

Jul 14, 2021

Genome-Nilou Lab

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

-0.92

CADD

Benign

0.093

DANN

Benign

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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