15-50182561-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003645.4(SLC27A2):c.134G>A(p.Ser45Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,612,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

SLC27A2
NM_003645.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.236

Variant links:

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]

SLC27A2 links:

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]

ATP8B4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13356698).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC27A2	NM_003645.4 link	c.134G>A	p.Ser45Asn	missense_variant	Exon 1 of 10	ENST00000267842.10	NP_003636.2	O14975-1
SLC27A2	NM_001159629.2 link	c.134G>A	p.Ser45Asn	missense_variant	Exon 1 of 9		NP_001153101.1	O14975-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC27A2	ENST00000267842.10 link	c.134G>A	p.Ser45Asn	missense_variant	Exon 1 of 10	1	NM_003645.4	ENSP00000267842.5	O14975-1
SLC27A2	ENST00000380902.8 link	c.134G>A	p.Ser45Asn	missense_variant	Exon 1 of 9	1		ENSP00000370289.4	O14975-2
ATP8B4	ENST00000558829.1 link	c.-343C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 4	3		ENSP00000453539.1	H0YMB5
ATP8B4	ENST00000558829.1 link	c.-343C>T		5_prime_UTR_variant	Exon 1 of 4	3		ENSP00000453539.1	H0YMB5

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000819

AC:

AN:

244064

Hom.:

AF XY:

0.00

AC XY:

AN XY:

132776

show subpopulations

Gnomad AFR exome

AF:

0.000128

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.0000110

AC:

AN:

1460656

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

726622

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000604

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.134G>A (p.S45N) alteration is located in exon 1 (coding exon 1) of the SLC27A2 gene. This alteration results from a G to A substitution at nucleotide position 134, causing the serine (S) at amino acid position 45 to be replaced by an asparagine (N). 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

0.095

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.18

T;.

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.31

T;T

M_CAP

Benign

0.061

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.5

M;M

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.83

N;N

REVEL

Benign

0.19

Sift

Benign

0.50

T;T

Sift4G

Benign

0.52

T;T

Polyphen

0.29

B;.

Vest4

0.074

MutPred

0.36

Gain of helix (P = 0.0117);Gain of helix (P = 0.0117);

MVP

0.55

MPC

0.67

ClinPred

0.080

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.48

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over