dbSNP rs777652108: SLC27A2:p.Pro51Gln (chr15-50182579-C-A) – ACMG Classification: Uncertain_significance (2 pts)

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

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]

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:

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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
SLC27A2	NM_003645.4 link	c.152C>A	p.Pro51Gln	missense_variant	Exon 1 of 10	ENST00000267842.10	NP_003636.2	O14975-1
SLC27A2	NM_001159629.2 link	c.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	UniProt
SLC27A2	ENST00000267842.10 link	c.152C>A	p.Pro51Gln	missense_variant	Exon 1 of 10	1	NM_003645.4	ENSP00000267842.5	O14975-1
SLC27A2	ENST00000380902.8 link	c.152C>A	p.Pro51Gln	missense_variant	Exon 1 of 9	1		ENSP00000370289.4	O14975-2
ATP8B4	ENST00000558829.1 link	c.-361G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 4	3		ENSP00000453539.1	H0YMB5
ATP8B4	ENST00000558829.1 link	c.-361G>T		5_prime_UTR_variant	Exon 1 of 4	3		ENSP00000453539.1	H0YMB5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000418

AC:

AN:

239518

Hom.:

AF XY:

0.00000764

AC XY:

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:

AN:

1459662

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

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.:

Asia WGS

AF:

0.000578

AC:

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

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.54

D;.

Eigen

Benign

0.10

Eigen_PC

Benign

0.036

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.59

T;T

M_CAP

Benign

0.055

MetaRNN

Uncertain

0.48

T;T

MetaSVM

Benign

-0.80

MutationAssessor

Uncertain

2.2

M;M

PrimateAI

Uncertain

0.54

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over