10-112376369-G-A

Variant names:

• chr10-112376369-G-A
• rs1363751167
• ENST00000356116.6:c.60G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_016234.4(ACSL5):​c.60G>A​(p.Arg20Arg) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACSL5 NM_016234.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• diarrhea 13

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=0.225 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016234.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSL5	NM_203379.2	MANE Select	c.-30+2100G>A		intron	N/A	NP_976313.1	Q9ULC5-1
	ACSL5	NM_016234.4		c.60G>A	p.Arg20Arg	synonymous	Exon 1 of 21	NP_057318.2
	ACSL5	NM_001387037.1		c.60G>A	p.Arg20Arg	synonymous	Exon 1 of 20	NP_001373966.1	A0A8C8L3F5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSL5	ENST00000356116.6	TSL:1	c.60G>A	p.Arg20Arg	synonymous	Exon 1 of 21	ENSP00000348429.1	Q9ULC5-3
	ACSL5	ENST00000354273.5	TSL:1	c.60G>A	p.Arg20Arg	synonymous	Exon 1 of 19	ENSP00000346223.5	A0A8C8KCK5
	ACSL5	ENST00000354655.9	TSL:2 MANE Select	c.-30+2100G>A		intron	N/A	ENSP00000346680.4	Q9ULC5-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.0
DANN	Benign	0.67
PhyloP100		0.23
PromoterAI		-0.0058	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1363751167; hg19: chr10-114136127;