Variant 16-89098577-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001243279.3(ACSF3):c.-193-14A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 449,106 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 34)

Exomes 𝑓: 0.0016 ( 1 hom. )

Consequence

ACSF3
NM_001243279.3 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.94

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 Likely_benign. Variant got -6 ACMG points.

BP4

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

BP6

Variant 16-89098577-A-G is Benign according to our data. Variant chr16-89098577-A-G is described in ClinVar as [Benign]. Clinvar id is 377429.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSF3	NM_001243279.3 linkuse as main transcript	c.-193-14A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000614302.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSF3	ENST00000614302.5 linkuse as main transcript	c.-193-14A>G		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001243279.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00138

AC:

210

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00179

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00149

AC:

191

AN:

127856

Hom.:

AF XY:

0.00149

AC XY:

104

AN XY:

69854

show subpopulations

Gnomad AFR exome

AF:

0.000164

Gnomad AMR exome

AF:

0.00181

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000452

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00261

Gnomad OTH exome

AF:

0.00278

GnomAD4 exome

AF:

0.00156

AC:

462

AN:

296738

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

250

AN XY:

168524

show subpopulations

Gnomad4 AFR exome

AF:

0.000236

Gnomad4 AMR exome

AF:

0.00180

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000505

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00229

Gnomad4 OTH exome

AF:

0.00173

GnomAD4 genome

AF:

0.00137

AC:

209

AN:

152368

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

101

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00411

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00179

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00197

Hom.:

Bravo

AF:

0.00220

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 17, 2015

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

Cadd

Benign

1.9

Dann

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

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