Variant 10-112409597-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_203379.2(ACSL5):c.623T>A(p.Val208Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ACSL5
NM_203379.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.00

Variant links:

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]

ACSL5 links:

ENSG00000232934 (HGNC:):

ENSG00000232934 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10594487).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACSL5	NM_203379.2 linkuse as main transcript	c.623T>A	p.Val208Glu	missense_variant	7/21	ENST00000354655.9	NP_976313.1	Q9ULC5-1
ACSL5	NM_016234.4 linkuse as main transcript	c.791T>A	p.Val264Glu	missense_variant	7/21		NP_057318.2	Q9ULC5-3
ACSL5	NM_001387037.1 linkuse as main transcript	c.791T>A	p.Val264Glu	missense_variant	7/20		NP_001373966.1
ACSL5	NM_203380.2 linkuse as main transcript	c.623T>A	p.Val208Glu	missense_variant	7/21		NP_976314.1	Q9ULC5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSL5	ENST00000354655.9 linkuse as main transcript	c.623T>A	p.Val208Glu	missense_variant	7/21	2	NM_203379.2	ENSP00000346680.4		Q9ULC5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251408

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461832

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727218

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Oct 14, 2023

The c.791T>A (p.V264E) alteration is located in exon 7 (coding exon 7) of the ACSL5 gene. This alteration results from a T to A substitution at nucleotide position 791, causing the valine (V) at amino acid position 264 to be replaced by a glutamic acid (E). 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

0.18

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.036

T;T;.;.;T

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.22

LIST_S2

Uncertain

0.90

.;D;D;D;.

M_CAP

Benign

0.014

MetaRNN

Benign

0.11

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.17

N;N;.;N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.1

N;N;N;N;N

REVEL

Benign

0.050

Sift

Benign

0.28

T;T;T;T;T

Sift4G

Benign

0.27

T;T;T;T;T

Polyphen

0.046

B;B;B;.;B

Vest4

0.30

MutPred

0.64

Loss of methylation at K207 (P = 0.0376);Loss of methylation at K207 (P = 0.0376);.;Loss of methylation at K207 (P = 0.0376);Loss of methylation at K207 (P = 0.0376);

MVP

0.46

MPC

0.37

ClinPred

0.067

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

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

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