16-89093750-G-C

Variant names:

• chr16-89093750-G-C
• rs76688594
• ENST00000537895.5:c.-130+5272G>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.242

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]

ACMG classification

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSF3	ENST00000537895.5	c.-130+5272G>C		intron_variant	Intron 1 of 3	4		ENSP00000439201.1

Frequencies

GnomAD3 genomes AF: 0.688 AC: 103760 AN: 150762 Hom.: 36502 Cov.: 31

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

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.: 31 AF XY: 0.690 AC XY: 50855 AN XY: 73702

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

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

Other links and lift over

dbSNP: rs76688594; hg19: chr16-89160158;