16-89093755-G-A

Variant names:

• chr16-89093755-G-A
• rs10163232
• ENST00000537895.5:c.-130+5277G>A

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+5277G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0283 in 152,708 control chromosomes in the GnomAD database, including 176 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (174 hom., cov: 32)
  • Exomes 𝑓: 0.020 (2 hom.)
• Consequence: ACSF3 ENST00000537895.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.44

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=-0.85).
• BP6: Variant 16-89093755-G-A is Benign according to our data. Variant chr16-89093755-G-A is described in ClinVar as [Benign]. Clinvar id is 1234159.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0903 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+5277G>A		intron_variant	Intron 1 of 3	4		ENSP00000439201.1

Frequencies

GnomAD3 genomes AF: 0.0283 AC: 4271 AN: 151162 Hom.: 172 Cov.: 32

Gnomad AFR AF: 0.0925

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0136

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0352

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000502

Gnomad OTH AF: 0.0208

GnomAD4 exome AF: 0.0202 AC: 29 AN: 1438 Hom.: 2 AF XY: 0.0237 AC XY: 23 AN XY: 970

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.233

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00249

Gnomad4 OTH exome AF: 0.0172

GnomAD4 genome AF: 0.0284 AC: 4294 AN: 151270 Hom.: 174 Cov.: 32 AF XY: 0.0282 AC XY: 2088 AN XY: 73924

Gnomad4 AFR AF: 0.0928

Gnomad4 AMR AF: 0.0136

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0352

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000502

Gnomad4 OTH AF: 0.0205

Alfa AF: 0.0221 Hom.: 15

Bravo AF: 0.0315

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 24, 2021

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	-0.85
CADD	Benign	2.1
DANN	Benign	0.74

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10163232; hg19: chr16-89160163;