Variant 2-222916468-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_004457.5(ACSL3):c.528A>G(p.Ala176Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00615 in 1,611,758 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0047 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0063 ( 25 hom. )

Consequence

ACSL3
NM_004457.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.21

Variant links:

Genes affected

ACSL3 (HGNC:3570): (acyl-CoA synthetase long chain family member 3) The protein encoded by this gene is an isozyme of the long-chain fatty-acid-coenzyme A ligase family. Although differing in substrate specificity, subcellular localization, and tissue distribution, all isozymes of this family convert free long-chain fatty acids into fatty acyl-CoA esters, and thereby play a key role in lipid biosynthesis and fatty acid degradation. This isozyme is highly expressed in brain, and preferentially utilizes myristate, arachidonate, and eicosapentaenoate as substrates. The amino acid sequence of this isozyme is 92% identical to that of rat homolog. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ACSL3 links:

ACSL3 (HGNC:):

ACSL3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 2-222916468-A-G is Benign according to our data. Variant chr2-222916468-A-G is described in ClinVar as [Benign]. Clinvar id is 777142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.21 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACSL3	NM_004457.5 linkuse as main transcript	c.528A>G	p.Ala176Ala	synonymous_variant	5/17	ENST00000357430.8	NP_004448.2	O95573A0A024R487
ACSL3	NM_001354158.2 linkuse as main transcript	c.528A>G	p.Ala176Ala	synonymous_variant	4/16		NP_001341087.1
ACSL3	NM_001354159.2 linkuse as main transcript	c.528A>G	p.Ala176Ala	synonymous_variant	3/15		NP_001341088.1
ACSL3	NM_203372.3 linkuse as main transcript	c.528A>G	p.Ala176Ala	synonymous_variant	4/16		NP_976251.1	O95573A0A024R487

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSL3	ENST00000357430.8 linkuse as main transcript	c.528A>G	p.Ala176Ala	synonymous_variant	5/17	1	NM_004457.5	ENSP00000350012.3		O95573

Frequencies

GnomAD3 genomes

AF:

0.00468

AC:

712

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00154

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00348

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00779

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00406

AC:

1017

AN:

250246

Hom.:

AF XY:

0.00407

AC XY:

551

AN XY:

135286

show subpopulations

Gnomad AFR exome

AF:

0.000739

Gnomad AMR exome

AF:

0.000585

Gnomad ASJ exome

AF:

0.00229

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000623

Gnomad FIN exome

AF:

0.00301

Gnomad NFE exome

AF:

0.00760

Gnomad OTH exome

AF:

0.00279

GnomAD4 exome

AF:

0.00630

AC:

9197

AN:

1459450

Hom.:

Cov.:

AF XY:

0.00608

AC XY:

4414

AN XY:

726078

show subpopulations

Gnomad4 AFR exome

AF:

0.000750

Gnomad4 AMR exome

AF:

0.000542

Gnomad4 ASJ exome

AF:

0.00269

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000698

Gnomad4 FIN exome

AF:

0.00277

Gnomad4 NFE exome

AF:

0.00776

Gnomad4 OTH exome

AF:

0.00402

GnomAD4 genome

AF:

0.00467

AC:

712

AN:

152308

Hom.:

Cov.:

AF XY:

0.00440

AC XY:

328

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00154

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00348

Gnomad4 NFE

AF:

0.00779

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00371

Hom.:

Bravo

AF:

0.00459

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

1.1

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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