rs8624

Variant names:

• chr10-112428029-T-C
• rs8624
• NM_203379.2:c.*671T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 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]

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203379.2. 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.*671T>C		3_prime_UTR	Exon 21 of 21	NP_976313.1	Q9ULC5-1
	ACSL5	NM_016234.4		c.*671T>C		3_prime_UTR	Exon 21 of 21	NP_057318.2
	ACSL5	NM_001387037.1		c.*671T>C		3_prime_UTR	Exon 20 of 20	NP_001373966.1	A0A8C8L3F5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSL5	ENST00000354655.9	TSL:2 MANE Select	c.*671T>C		3_prime_UTR	Exon 21 of 21	ENSP00000346680.4	Q9ULC5-1
	ACSL5	ENST00000356116.6	TSL:1	c.*671T>C		3_prime_UTR	Exon 21 of 21	ENSP00000348429.1	Q9ULC5-3
	ACSL5	ENST00000354273.5	TSL:1	c.*671T>C		3_prime_UTR	Exon 19 of 19	ENSP00000346223.5	A0A8C8KCK5

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

African (AFR) AF: 0.520 AC: 418 AN: 804

American (AMR) AF: 0.249 AC: 110 AN: 442

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 345 AN: 888

East Asian (EAS) AF: 0.297 AC: 361 AN: 1214

South Asian (SAS) AF: 0.375 AC: 42 AN: 112

European-Finnish (FIN) AF: 0.361 AC: 163 AN: 452

Middle Eastern (MID) AF: 0.406 AC: 39 AN: 96

European-Non Finnish (NFE) AF: 0.302 AC: 3290 AN: 10894

Other (OTH) AF: 0.300 AC: 388 AN: 1294

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

African (AFR) AF: 0.498 AC: 20672 AN: 41480

American (AMR) AF: 0.276 AC: 4225 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1467 AN: 3468

East Asian (EAS) AF: 0.328 AC: 1696 AN: 5166

South Asian (SAS) AF: 0.318 AC: 1534 AN: 4822

European-Finnish (FIN) AF: 0.346 AC: 3653 AN: 10564

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20282 AN: 67984

Other (OTH) AF: 0.351 AC: 741 AN: 2112

Alfa AF: 0.320 Hom.: 25328

Bravo AF: 0.359

Asia WGS AF: 0.322 AC: 1121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.49
PhyloP100		0.049
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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