15-50182579-C-A

Variant names:

• chr15-50182579-C-A
• rs777652108
• NM_003645.4:c.152C>A

Variant summary

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

The NM_003645.4(SLC27A2):​c.152C>A​(p.Pro51Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,662 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P51L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC27A2 NM_003645.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46

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.152C>A	p.Pro51Gln	missense_variant	Exon 1 of 10	ENST00000267842.10	NP_003636.2
SLC27A2	NM_001159629.2	c.152C>A	p.Pro51Gln	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.152C>A	p.Pro51Gln	missense_variant	Exon 1 of 10	1	NM_003645.4	ENSP00000267842.5
SLC27A2	ENST00000380902.8	c.152C>A	p.Pro51Gln	missense_variant	Exon 1 of 9	1		ENSP00000370289.4
ATP8B4	ENST00000558829.1	c.-361G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 4	3		ENSP00000453539.1
ATP8B4	ENST00000558829.1	c.-361G>T		5_prime_UTR_variant	Exon 1 of 4	3		ENSP00000453539.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000418 AC: 1 AN: 239518 Hom.: 0 AF XY: 0.00000764 AC XY: 1 AN XY: 130962

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 SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459662 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 726108

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000578 AC: 2 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.54	D;.
Eigen	Benign	0.10
Eigen_PC	Benign	0.036
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.59	T;T
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.2	M;M
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.4	D;D
REVEL	Benign	0.25
Sift	Uncertain	0.016	D;D
Sift4G	Benign	0.088	T;T
Polyphen		1.0	D;.
Vest4		0.47
MutPred		0.49		Loss of glycosylation at P51 (P = 0.0095);Loss of glycosylation at P51 (P = 0.0095);
MVP		0.60
MPC		1.7
ClinPred		0.97	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.32
gMVP		0.68

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

LitVar

Other links and lift over

dbSNP: rs777652108; hg19: chr15-50474776;