dbSNP rs76688594: ACSF3:c.-130+5272G>C (chr16-89093750-G-C) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The ENST00000537895.5(ACSF3):c.-130+5272G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 151,926 control chromosomes in the GnomAD database, including 36,819 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.69 ( 36521 hom., cov: 31)

Exomes 𝑓: 0.75 ( 298 hom. )

Consequence

ACSF3
ENST00000537895.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.242

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

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

BP6

Variant 16-89093750-G-C is Benign according to our data. Variant chr16-89093750-G-C is described in ClinVar as [Benign]. Clinvar id is 1266611.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSF3	NM_001243279.3 link	c.-440G>C		upstream_gene_variant		ENST00000614302.5	NP_001230208.1	Q4G176

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSF3	ENST00000614302.5 link	c.-440G>C		upstream_gene_variant		5	NM_001243279.3	ENSP00000479130.1		Q4G176

Frequencies

GnomAD3 genomes

AF:

0.688

AC:

103760

AN:

150762

Hom.:

36502

Cov.:

show subpopulations

Gnomad AFR

AF:

0.530

Gnomad AMI

AF:

0.613

Gnomad AMR

AF:

0.755

Gnomad ASJ

AF:

0.630

Gnomad EAS

AF:

0.817

Gnomad SAS

AF:

0.740

Gnomad FIN

AF:

0.736

Gnomad MID

AF:

0.713

Gnomad NFE

AF:

0.753

Gnomad OTH

AF:

0.701

GnomAD4 exome

AF:

0.748

AC:

790

AN:

1056

Hom.:

298

AF XY:

0.742

AC XY:

540

AN XY:

728

show subpopulations

Gnomad4 AFR exome

AF:

0.500

Gnomad4 AMR exome

AF:

1.00

Gnomad4 ASJ exome

AF:

0.250

Gnomad4 EAS exome

AF:

0.792

Gnomad4 SAS exome

AF:

0.580

Gnomad4 FIN exome

AF:

0.833

Gnomad4 NFE exome

AF:

0.759

Gnomad4 OTH exome

AF:

0.800

GnomAD4 genome

AF:

0.688

AC:

103809

AN:

150870

Hom.:

36521

Cov.:

AF XY:

0.690

AC XY:

50855

AN XY:

73702

show subpopulations

Gnomad4 AFR

AF:

0.529

Gnomad4 AMR

AF:

0.756

Gnomad4 ASJ

AF:

0.630

Gnomad4 EAS

AF:

0.816

Gnomad4 SAS

AF:

0.742

Gnomad4 FIN

AF:

0.736

Gnomad4 NFE

AF:

0.753

Gnomad4 OTH

AF:

0.705

Alfa

AF:

0.710

Hom.:

4732

Bravo

AF:

0.685

Asia WGS

AF:

0.756

AC:

2493

AN:

3296

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

-0.83

CADD

Benign

4.0

DANN

Benign

0.25

Splicing

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