15-50202549-G-A

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003645.4(SLC27A2):c.751G>A(p.Val251Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,614,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SLC27A2
NM_003645.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.23

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06436491).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC27A2	NM_003645.4 link	c.751G>A	p.Val251Ile	missense_variant	Exon 3 of 10	ENST00000267842.10	NP_003636.2	O14975-1
SLC27A2	NM_001159629.2 link	c.689-2690G>A		intron_variant	Intron 2 of 8		NP_001153101.1	O14975-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC27A2	ENST00000267842.10 link	c.751G>A	p.Val251Ile	missense_variant	Exon 3 of 10	1	NM_003645.4	ENSP00000267842.5	O14975-1
SLC27A2	ENST00000380902.8 link	c.689-2690G>A		intron_variant	Intron 2 of 8	1		ENSP00000370289.4	O14975-2
SLC27A2	ENST00000544960.1 link	c.46G>A	p.Val16Ile	missense_variant	Exon 4 of 11	2		ENSP00000444549.1	G3V1R7

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.00000398

AC:

AN:

251448

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135894

show subpopulations

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461860

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0000483

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

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 29, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.751G>A (p.V251I) alteration is located in exon 3 (coding exon 3) of the SLC27A2 gene. This alteration results from a G to A substitution at nucleotide position 751, causing the valine (V) at amino acid position 251 to be replaced by an isoleucine (I). 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

0.081

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.011

DANN

Benign

0.39

DEOGEN2

Benign

0.071

T;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.33

T;T

M_CAP

Benign

0.0022

MetaRNN

Benign

0.064

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.36

N;.

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.15

N;N

REVEL

Benign

0.032

Sift

Benign

0.64

T;T

Sift4G

Benign

0.63

T;T

Polyphen

0.0

B;.

Vest4

0.078

MutPred

0.43

Gain of helix (P = 0.132);.;

MVP

0.040

MPC

0.048

ClinPred

0.024

GERP RS

-11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.022

gMVP

0.20

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