Variant 2-222908805-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_004457.5(ACSL3):c.33C>T(p.Thr11Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00412 in 1,602,950 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0038 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 36 hom. )

Consequence

ACSL3
NM_004457.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.391

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 2-222908805-C-T is Benign according to our data. Variant chr2-222908805-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 712051.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.391 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACSL3	NM_004457.5 linkuse as main transcript	c.33C>T	p.Thr11Thr	synonymous_variant	4/17	ENST00000357430.8	NP_004448.2	O95573A0A024R487
ACSL3	NM_001354158.2 linkuse as main transcript	c.33C>T	p.Thr11Thr	synonymous_variant	3/16		NP_001341087.1
ACSL3	NM_001354159.2 linkuse as main transcript	c.33C>T	p.Thr11Thr	synonymous_variant	2/15		NP_001341088.1
ACSL3	NM_203372.3 linkuse as main transcript	c.33C>T	p.Thr11Thr	synonymous_variant	3/16		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.33C>T	p.Thr11Thr	synonymous_variant	4/17	1	NM_004457.5	ENSP00000350012.3		O95573

Frequencies

GnomAD3 genomes

AF:

0.00385

AC:

585

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00720

Gnomad ASJ

AF:

0.0369

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00432

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00459

AC:

1108

AN:

241584

Hom.:

AF XY:

0.00471

AC XY:

617

AN XY:

130976

show subpopulations

Gnomad AFR exome

AF:

0.000396

Gnomad AMR exome

AF:

0.00340

Gnomad ASJ exome

AF:

0.0395

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000958

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.00468

Gnomad OTH exome

AF:

0.00829

GnomAD4 exome

AF:

0.00415

AC:

6014

AN:

1450704

Hom.:

Cov.:

AF XY:

0.00426

AC XY:

3075

AN XY:

721188

show subpopulations

Gnomad4 AFR exome

AF:

0.000796

Gnomad4 AMR exome

AF:

0.00349

Gnomad4 ASJ exome

AF:

0.0385

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000879

Gnomad4 FIN exome

AF:

0.000450

Gnomad4 NFE exome

AF:

0.00387

Gnomad4 OTH exome

AF:

0.00607

GnomAD4 genome

AF:

0.00383

AC:

583

AN:

152246

Hom.:

Cov.:

AF XY:

0.00402

AC XY:

299

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.00713

Gnomad4 ASJ

AF:

0.0369

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.00432

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00642

Hom.:

Bravo

AF:

0.00445

Asia WGS

AF:

0.000289

AC:

AN:

3474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	ACSL3: BP4, BP7 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

9.6

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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