10-112398947-G-A

Variant names:

• chr10-112398947-G-A
• rs746731885
• NM_203379.2:c.203G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_203379.2(ACSL5):​c.203G>A​(p.Ser68Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/24 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. S68T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ACSL5 NM_203379.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570
• 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)

ENSG00000232934 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.203G>A	p.Ser68Asn	missense	Exon 3 of 21	NP_976313.1	Q9ULC5-1
	ACSL5	NM_016234.4		c.371G>A	p.Ser124Asn	missense	Exon 3 of 21	NP_057318.2
	ACSL5	NM_001387037.1		c.371G>A	p.Ser124Asn	missense	Exon 3 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.203G>A	p.Ser68Asn	missense	Exon 3 of 21	ENSP00000346680.4	Q9ULC5-1
	ACSL5	ENST00000356116.6	TSL:1	c.371G>A	p.Ser124Asn	missense	Exon 3 of 21	ENSP00000348429.1	Q9ULC5-3
	ACSL5	ENST00000354273.5	TSL:1	c.371G>A	p.Ser124Asn	missense	Exon 3 of 19	ENSP00000346223.5	A0A8C8KCK5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251444 AF XY: 0.00

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461838 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727220

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111984

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.5
DANN	Benign	0.74
DEOGEN2	Benign	0.046	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		-0.057
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.015
Sift	Benign	0.20	T
Sift4G	Benign	0.22	T
Polyphen		0.0020	B
Vest4		0.23
MutPred		0.26		Loss of disorder (P = 0.1585)
MVP		0.37
MPC		0.16
ClinPred		0.031	T
GERP RS		-8.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.045
gMVP		0.28
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.21		Position offset: -46

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

Other links and lift over

dbSNP: rs746731885; hg19: chr10-114158705; COSMIC: COSV105259821;