15-50182594-T-C

Variant names:

• chr15-50182594-T-C
• NM_003645.4:c.167T>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003645.4(SLC27A2):​c.167T>C​(p.Leu56Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,024 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SLC27A2 NM_003645.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.62

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC27A2	NM_003645.4	c.167T>C	p.Leu56Pro	missense_variant	Exon 1 of 10	ENST00000267842.10	NP_003636.2
SLC27A2	NM_001159629.2	c.167T>C	p.Leu56Pro	missense_variant	Exon 1 of 9		NP_001153101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC27A2	ENST00000267842.10	c.167T>C	p.Leu56Pro	missense_variant	Exon 1 of 10	1	NM_003645.4	ENSP00000267842.5
SLC27A2	ENST00000380902.8	c.167T>C	p.Leu56Pro	missense_variant	Exon 1 of 9	1		ENSP00000370289.4
ATP8B4	ENST00000558829.1	c.-376A>G		5_prime_UTR_variant	Exon 1 of 4	3		ENSP00000453539.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461024 Hom.: 0 Cov.: 36 AF XY: 0.00000413 AC XY: 3 AN XY: 726848

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.167T>C (p.L56P) alteration is located in exon 1 (coding exon 1) of the SLC27A2 gene. This alteration results from a T to C substitution at nucleotide position 167, causing the leucine (L) at amino acid position 56 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.59	D;.
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.060	D
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.7	M;M
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-5.4	D;D
REVEL	Benign	0.29
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.043	D;D
Polyphen		0.91	P;.
Vest4		0.46
MutPred		0.70		Gain of disorder (P = 0.0177);Gain of disorder (P = 0.0177);
MVP		0.52
MPC		1.3
ClinPred		0.97	D
GERP RS		3.8
Varity_R		0.66
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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-50474791;