19-3178827-C-T

Variant summary

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

The NM_003775.4(S1PR4):​c.35C>T​(p.Ser12Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

S1PR4
NM_003775.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.15
Variant links:
Genes affected
S1PR4 (HGNC:3170): (sphingosine-1-phosphate receptor 4) This gene is a member of the endothelial differentiation, G-protein-coupled (EDG)) receptor gene family. EDG receptors bind lysophospholipids or lysosphingolipids as ligands, and are involved in cell signalling in many different cell types. This EDG receptor gene is intronless and is specifically expressed in the lymphoid tissue. [provided by RefSeq, Jul 2008]

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=0.12628955).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
S1PR4NM_003775.4 linkc.35C>T p.Ser12Phe missense_variant Exon 1 of 1 ENST00000246115.5 NP_003766.1 O95977

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
S1PR4ENST00000246115.5 linkc.35C>T p.Ser12Phe missense_variant Exon 1 of 1 6 NM_003775.4 ENSP00000246115.3 O95977
S1PR4ENST00000591346.1 linkn.100-387C>T intron_variant Intron 1 of 1 3
ENSG00000289471ENST00000687895.2 linkn.-119G>A upstream_gene_variant

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1381788
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
682892
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 20, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.35C>T (p.S12F) alteration is located in exon 1 (coding exon 1) of the S1PR4 gene. This alteration results from a C to T substitution at nucleotide position 35, causing the serine (S) at amino acid position 12 to be replaced by a phenylalanine (F). 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
0.12
BayesDel_addAF
Benign
-0.048
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
16
DANN
Benign
0.97
DEOGEN2
Benign
0.061
T
Eigen
Benign
-0.41
Eigen_PC
Benign
-0.28
FATHMM_MKL
Benign
0.65
D
LIST_S2
Benign
0.51
T
M_CAP
Uncertain
0.10
D
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-0.82
T
MutationAssessor
Benign
1.3
L
PrimateAI
Uncertain
0.70
T
PROVEAN
Benign
-0.66
N
REVEL
Benign
0.17
Sift
Benign
0.37
T
Sift4G
Benign
0.32
T
Polyphen
0.0030
B
Vest4
0.23
MutPred
0.27
Loss of disorder (P = 0.0171);
MVP
0.19
MPC
0.45
ClinPred
0.45
T
GERP RS
2.3
Varity_R
0.10
gMVP
0.74

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-3178825; API