15-50197584-C-G

Variant names:

• chr15-50197584-C-G
• rs1440271430
• NM_003645.4:c.563C>G

Variant summary

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

The NM_003645.4(SLC27A2):​c.563C>G​(p.Thr188Arg) 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 1,461,590 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC27A2 NM_003645.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.904
• Publications: 1 publications found

Genes affected

SLC27A2 (HGNC:10996): (solute carrier family 27 member 2) The protein encoded by this gene is an isozyme of 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 activates long-chain, branched-chain and very-long-chain fatty acids containing 22 or more carbons to their CoA derivatives. It is expressed primarily in liver and kidney, and is present in both endoplasmic reticulum and peroxisomes, but not in mitochondria. Its decreased peroxisomal enzyme activity is in part responsible for the biochemical pathology in X-linked adrenoleukodystrophy. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2009]

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_003645.4. 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
	SLC27A2	NM_003645.4	MANE Select	c.563C>G	p.Thr188Arg	missense	Exon 2 of 10	NP_003636.2	O14975-1
	SLC27A2	NM_001159629.2		c.563C>G	p.Thr188Arg	missense	Exon 2 of 9	NP_001153101.1	O14975-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC27A2	ENST00000267842.10	TSL:1 MANE Select	c.563C>G	p.Thr188Arg	missense	Exon 2 of 10	ENSP00000267842.5	O14975-1
	SLC27A2	ENST00000380902.8	TSL:1	c.563C>G	p.Thr188Arg	missense	Exon 2 of 9	ENSP00000370289.4	O14975-2
	SLC27A2	ENST00000895509.1		c.563C>G	p.Thr188Arg	missense	Exon 2 of 11	ENSP00000565568.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000795 AC: 2 AN: 251456 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

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: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461590 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727122

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111782

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.21
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.90
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.17
Sift	Benign	0.092	T
Sift4G	Benign	0.35	T
Polyphen		0.98	D
Vest4		0.59
MutPred		0.53		Gain of phosphorylation at T185 (P = 0.0652)
MVP		0.52
MPC		0.36
ClinPred		0.86	D
GERP RS		5.5
Varity_R		0.30
gMVP		0.59
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1440271430; hg19: chr15-50489781;