Variant 5-131988868-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001009185.3(ACSL6):c.589A>G(p.Met197Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ACSL6
NM_001009185.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.89

Variant links:

Genes affected

ACSL6 (HGNC:16496): (acyl-CoA synthetase long chain family member 6) The protein encoded by this gene catalyzes the formation of acyl-CoA from fatty acids, ATP, and CoA, using magnesium as a cofactor. The encoded protein plays a major role in fatty acid metabolism in the brain. Translocations with the ETV6 gene are causes of myelodysplastic syndrome with basophilia, acute myelogenous leukemia with eosinophilia, and acute eosinophilic leukemia. Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Apr 2011]

ACSL6 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSL6	NM_001009185.3 linkuse as main transcript	c.589A>G	p.Met197Val	missense_variant	6/21	ENST00000651883.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSL6	ENST00000651883.2 linkuse as main transcript	c.589A>G	p.Met197Val	missense_variant	6/21		NM_001009185.3	A1	Q9UKU0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461842

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 26, 2024

The c.589A>G (p.M197V) alteration is located in exon 6 (coding exon 6) of the ACSL6 gene. This alteration results from a A to G substitution at nucleotide position 589, causing the methionine (M) at amino acid position 197 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.070

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

D;D;.;D;D;D;D;D;D;.;D

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.58

D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.74

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-2.9

D;D;D;D;D;D;D;D;D;D;D

REVEL

Benign

0.27

Sift

Uncertain

0.0070

D;D;D;D;D;D;D;D;D;D;D

Sift4G

Benign

0.091

T;T;T;T;T;T;D;T;T;T;D

Polyphen

0.88

P;P;P;P;.;P;P;P;.;.;.

Vest4

0.86

MutPred

0.58

.;.;.;.;.;Gain of catalytic residue at M172 (P = 0.0997);Gain of catalytic residue at M172 (P = 0.0997);Gain of catalytic residue at M172 (P = 0.0997);.;.;Gain of catalytic residue at M172 (P = 0.0997);

MVP

0.71

MPC

1.1

ClinPred

0.97

GERP RS

5.8

Varity_R

0.52

gMVP

0.61

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over