X-109683270-T-C

Position:

• chrX-109683270-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001318510.2(ACSL4):​c.94A>G​(p.Ile32Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: ACSL4 NM_001318510.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.64

Genes affected

ACSL4 (HGNC:3571): (acyl-CoA synthetase long chain family member 4) 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 preferentially utilizes arachidonate as substrate. The absence of this enzyme may contribute to the cognitive disability or Alport syndrome. Alternative splicing of this gene generates multiple transcript variants. [provided by RefSeq, Jan 2016]

ACSL4 (HGNC:):

ACMG classification

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=0.117851526).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACSL4	NM_001318510.2	c.94A>G	p.Ile32Val	missense_variant	3/16	ENST00000672401.1	NP_001305439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSL4	ENST00000672401.1	c.94A>G	p.Ile32Val	missense_variant	3/16		NM_001318510.2	ENSP00000500273.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD3 exomes AF: 0.00000545 AC: 1 AN: 183358 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 67830

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: 0.0000122

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 06, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	16
DANN	Benign	0.91
DEOGEN2	Benign	0.097	T;T;.;.;.;T;.
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.70	.;T;T;T;T;T;T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.12	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;N;.;.;.;.;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.060	N;N;N;N;N;N;N
REVEL	Benign	0.097
Sift	Benign	0.52	T;T;T;T;T;T;T
Sift4G	Benign	0.51	T;T;T;.;T;T;.
Polyphen		0.0010	B;B;.;.;.;.;.
Vest4		0.11
MutPred		0.47		Gain of helix (P = 0.132);Gain of helix (P = 0.132);.;.;Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);
MVP		0.45
MPC		0.48
ClinPred		0.11	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs767663900; hg19: chrX-108926499;