rs137853133

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5

The NM_005094.4(SLC27A4):ā€‹c.739T>Cā€‹(p.Ser247Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. S247S) has been classified as Likely benign.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)

Consequence

SLC27A4
NM_005094.4 missense

Scores

13
5
1

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.67
Variant links:
Genes affected
SLC27A4 (HGNC:10998): (solute carrier family 27 member 4) This gene encodes a member of a family of fatty acid transport proteins, which are involved in translocation of long-chain fatty acids cross the plasma membrane. This protein is expressed at high levels on the apical side of mature enterocytes in the small intestine, and appears to be the principal fatty acid transporter in enterocytes. Clinical studies suggest this gene as a candidate gene for the insulin resistance syndrome. Mutations in this gene have been associated with ichthyosis prematurity syndrome. [provided by RefSeq, Apr 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.989
PP5
Variant 9-128350335-T-C is Pathogenic according to our data. Variant chr9-128350335-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 5745.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC27A4NM_005094.4 linkuse as main transcriptc.739T>C p.Ser247Pro missense_variant 5/13 ENST00000300456.5
SLC27A4XM_047422664.1 linkuse as main transcriptc.772T>C p.Ser258Pro missense_variant 5/13
SLC27A4XM_017014222.2 linkuse as main transcriptc.739T>C p.Ser247Pro missense_variant 6/14
SLC27A4XM_024447391.2 linkuse as main transcriptc.739T>C p.Ser247Pro missense_variant 6/14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC27A4ENST00000300456.5 linkuse as main transcriptc.739T>C p.Ser247Pro missense_variant 5/131 NM_005094.4 P1Q6P1M0-1
SLC27A4ENST00000372870.5 linkuse as main transcriptc.232-4843T>C intron_variant 1 Q6P1M0-2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152216
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
32
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152216
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Ichthyosis prematurity syndrome Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMAug 01, 2009- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.45
D
BayesDel_noAF
Pathogenic
0.41
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.63
D
Eigen
Pathogenic
0.81
Eigen_PC
Uncertain
0.64
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.91
D
M_CAP
Uncertain
0.25
D
MetaRNN
Pathogenic
0.99
D
MetaSVM
Pathogenic
0.94
D
MutationAssessor
Pathogenic
4.4
H
MutationTaster
Benign
1.0
A;A
PrimateAI
Pathogenic
0.81
D
PROVEAN
Pathogenic
-4.9
D
REVEL
Pathogenic
0.93
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.99
MutPred
0.95
Loss of glycosylation at S247 (P = 0.0446);
MVP
0.94
MPC
1.1
ClinPred
1.0
D
GERP RS
5.1
Varity_R
0.99
gMVP
0.87

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: rs137853133; hg19: chr9-131112614; API