15-50182579-C-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

Scores

7
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.46
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]
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]

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ACMG classification

Classification made for transcript

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
SLC27A2NM_003645.4 linkc.152C>A p.Pro51Gln missense_variant Exon 1 of 10 ENST00000267842.10 NP_003636.2 O14975-1
SLC27A2NM_001159629.2 linkc.152C>A p.Pro51Gln missense_variant Exon 1 of 9 NP_001153101.1 O14975-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC27A2ENST00000267842.10 linkc.152C>A p.Pro51Gln missense_variant Exon 1 of 10 1 NM_003645.4 ENSP00000267842.5 O14975-1
SLC27A2ENST00000380902.8 linkc.152C>A p.Pro51Gln missense_variant Exon 1 of 9 1 ENSP00000370289.4 O14975-2
ATP8B4ENST00000558829.1 linkc.-361G>T 5_prime_UTR_premature_start_codon_gain_variant Exon 1 of 4 3 ENSP00000453539.1 H0YMB5
ATP8B4ENST00000558829.1 linkc.-361G>T 5_prime_UTR_variant Exon 1 of 4 3 ENSP00000453539.1 H0YMB5

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
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:
0.0000328
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
show subpopulations
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

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

Other links and lift over

dbSNP: rs777652108; hg19: chr15-50474776; API