rs8624

Positions:

• chr10-112428029-T-C
• chr10-112428029-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_203379.2(ACSL5):​c.*671T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 168,290 control chromosomes in the GnomAD database, including 11,224 homozygotes. 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: 𝑓 0.36 (10383 hom., cov: 32)
  • Exomes 𝑓: 0.32 (841 hom.)
• Consequence: ACSL5 NM_203379.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490

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]

ZDHHC6 (HGNC:19160): (zinc finger DHHC-type palmitoyltransferase 6) Enables palmitoyltransferase activity. Involved in positive regulation of mitochondrial fusion and protein palmitoylation. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSL5	NM_203379.2	c.*671T>C		3_prime_UTR_variant	21/21	ENST00000354655.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSL5	ENST00000354655.9	c.*671T>C		3_prime_UTR_variant	21/21	2	NM_203379.2	P1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54514 AN: 151976 Hom.: 10368 Cov.: 32

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.349

GnomAD4 exome AF: 0.318 AC: 5156 AN: 16196 Hom.: 841 Cov.: 0 AF XY: 0.316 AC XY: 2552 AN XY: 8066

Gnomad4 AFR exome AF: 0.520

Gnomad4 AMR exome AF: 0.249

Gnomad4 ASJ exome AF: 0.389

Gnomad4 EAS exome AF: 0.297

Gnomad4 SAS exome AF: 0.375

Gnomad4 FIN exome AF: 0.361

Gnomad4 NFE exome AF: 0.302

Gnomad4 OTH exome AF: 0.300

GnomAD4 genome AF: 0.359 AC: 54584 AN: 152094 Hom.: 10383 Cov.: 32 AF XY: 0.359 AC XY: 26673 AN XY: 74334

Gnomad4 AFR AF: 0.498

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.423

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.351

Alfa AF: 0.316 Hom.: 10710

Bravo AF: 0.359

Asia WGS AF: 0.322 AC: 1121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.49

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: rs8624; hg19: chr10-114187787; COSMIC: COSV61133158; COSMIC: COSV61133158;