chr5-131988080-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001009185.3(ACSL6):c.799G>T(p.Gly267Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
ACSL6
NM_001009185.3 missense
NM_001009185.3 missense
Scores
8
7
2
Clinical Significance
Conservation
PhyloP100: 7.91
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.854
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACSL6 | NM_001009185.3 | c.799G>T | p.Gly267Trp | missense_variant | 7/21 | ENST00000651883.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACSL6 | ENST00000651883.2 | c.799G>T | p.Gly267Trp | missense_variant | 7/21 | NM_001009185.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 1AN: 152200Hom.: 0 Cov.: 33 FAILED QC
GnomAD3 genomes
?
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1
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33
FAILED QC
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251392Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135864
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461852Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727228
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.00000657 AC: 1AN: 152318Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74480
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Data not reliable, filtered out with message: AS_VQSR
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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 | Jan 30, 2024 | The c.799G>T (p.G267W) alteration is located in exon 7 (coding exon 7) of the ACSL6 gene. This alteration results from a G to T substitution at nucleotide position 799, causing the glycine (G) at amino acid position 267 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;.;D;D;D;D;D;D;.
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D;D;D;D;.;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D;D;D;D;D;.;D;D
Sift4G
Pathogenic
D;D;D;D;D;D;D;D;D;D
Polyphen
D;D;D;D;.;D;D;D;.;.
Vest4
MutPred
0.69
.;.;.;.;.;Gain of catalytic residue at G242 (P = 0.0075);Gain of catalytic residue at G242 (P = 0.0075);.;.;.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at