chr10-112416957-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_203379.2(ACSL5):c.1153G>A(p.Glu385Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,613,934 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
ACSL5
NM_203379.2 missense
NM_203379.2 missense
Scores
2
8
8
Clinical Significance
Conservation
PhyloP100: 9.89
Genes affected
ACSL5 (HGNC:16526): (acyl-CoA synthetase long chain family member 5) 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 uterus and spleen, and in trace amounts in normal brain, but has markedly increased levels in malignant gliomas. This gene functions in mediating fatty acid-induced glioma cell growth. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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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 |
---|---|---|---|---|---|---|---|
ACSL5 | NM_203379.2 | c.1153G>A | p.Glu385Lys | missense_variant | 13/21 | ENST00000354655.9 | |
ACSL5 | NM_016234.4 | c.1321G>A | p.Glu441Lys | missense_variant | 13/21 | ||
ACSL5 | NM_001387037.1 | c.1321G>A | p.Glu441Lys | missense_variant | 13/20 | ||
ACSL5 | NM_203380.2 | c.1153G>A | p.Glu385Lys | missense_variant | 13/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACSL5 | ENST00000354655.9 | c.1153G>A | p.Glu385Lys | missense_variant | 13/21 | 2 | NM_203379.2 | P1 | |
ENST00000631085.2 | n.175+1827C>T | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000658 AC: 10AN: 152066Hom.: 0 Cov.: 30
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251472Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135906
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461868Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727232
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GnomAD4 genome ? AF: 0.0000658 AC: 10AN: 152066Hom.: 0 Cov.: 30 AF XY: 0.0000808 AC XY: 6AN XY: 74256
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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 | Feb 15, 2023 | The c.1321G>A (p.E441K) alteration is located in exon 13 (coding exon 13) of the ACSL5 gene. This alteration results from a G to A substitution at nucleotide position 1321, causing the glutamic acid (E) at amino acid position 441 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T;.;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
M;M;.;M;M
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;D
REVEL
Benign
Sift
Benign
D;D;D;D;D
Sift4G
Benign
T;T;T;T;T
Polyphen
P;P;P;.;P
Vest4
MVP
MPC
0.66
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