ENST00000356116.6:c.88C>G

Variant names:

• chr10-112376397-C-G
• rs1250319285
• ENST00000356116.6:c.88C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000356116.6(ACSL5):​c.88C>G​(p.Pro30Ala) 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. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P30S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACSL5 ENST00000356116.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.344

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05087158).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSL5	NM_203379.2	c.-30+2128C>G		intron_variant	Intron 1 of 20	ENST00000354655.9	NP_976313.1
ACSL5	NM_016234.4	c.88C>G	p.Pro30Ala	missense_variant	Exon 1 of 21		NP_057318.2
ACSL5	NM_001387037.1	c.88C>G	p.Pro30Ala	missense_variant	Exon 1 of 20		NP_001373966.1
ACSL5	NM_203380.2	c.-30+855C>G		intron_variant	Intron 1 of 20		NP_976314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSL5	ENST00000354655.9	c.-30+2128C>G		intron_variant	Intron 1 of 20	2	NM_203379.2	ENSP00000346680.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	10
DANN	Uncertain	0.98
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.22	N
REVEL	Benign	0.048
Sift	Benign	0.038	D
Sift4G	Benign	0.23	T
Polyphen		0.0010	B
Vest4		0.19
MutPred		0.071		Loss of glycosylation at P30 (P = 0.0201);
MVP		0.10
MPC		0.49
ClinPred		0.89	D
GERP RS		0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
gMVP		0.066

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

Other links and lift over

dbSNP: rs1250319285; hg19: chr10-114136155;