15-50182759-T-G

Variant names:

• chr15-50182759-T-G
• rs776438530
• NM_003645.4:c.332T>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_003645.4(SLC27A2):​c.332T>G​(p.Met111Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC27A2 NM_003645.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.32
• Publications: 0 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]

ATP8B4 (HGNC:13536): (ATPase phospholipid transporting 8B4 (putative)) This gene encodes a member of the cation transport ATPase (P-type) family and type IV subfamily. The encoded protein is involved in phospholipid transport in the cell membrane. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.934

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.332T>G	p.Met111Arg	missense	Exon 1 of 10	NP_003636.2	O14975-1
	SLC27A2	NM_001159629.2		c.332T>G	p.Met111Arg	missense	Exon 1 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.332T>G	p.Met111Arg	missense	Exon 1 of 10	ENSP00000267842.5	O14975-1
	SLC27A2	ENST00000380902.8	TSL:1	c.332T>G	p.Met111Arg	missense	Exon 1 of 9	ENSP00000370289.4	O14975-2
	SLC27A2	ENST00000895509.1		c.332T>G	p.Met111Arg	missense	Exon 1 of 11	ENSP00000565568.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

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	Pathogenic	0.61
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.046	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		7.3
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.92	P
Vest4		0.74
MutPred		0.81		Loss of catalytic residue at M111 (P = 0.0056)
MVP		0.76
MPC		0.32
ClinPred		1.0	D
GERP RS		4.9
PromoterAI		-0.040	Neutral
Varity_R		0.88
gMVP		0.83

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: rs776438530; hg19: chr15-50474956;