1-101239703-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001400.5(S1PR1):c.719A>G(p.Asn240Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: S1PR1 NM_001400.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.93

Genes affected

S1PR1 (HGNC:3165): (sphingosine-1-phosphate receptor 1) The protein encoded by this gene is structurally similar to G protein-coupled receptors and is highly expressed in endothelial cells. It binds the ligand sphingosine-1-phosphate with high affinity and high specificity, and suggested to be involved in the processes that regulate the differentiation of endothelial cells. Activation of this receptor induces cell-cell adhesion. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

ACMG classification

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=0.13626033).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
S1PR1	NM_001400.5	c.719A>G	p.Asn240Ser	missense_variant	2/2	ENST00000305352.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
S1PR1	ENST00000305352.7	c.719A>G	p.Asn240Ser	missense_variant	2/2	1	NM_001400.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2022

The c.719A>G (p.N240S) alteration is located in exon 2 (coding exon 1) of the S1PR1 gene. This alteration results from a A to G substitution at nucleotide position 719, causing the asparagine (N) at amino acid position 240 to be replaced by a serine (S). 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	0.092
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
Cadd	Benign	19
Dann	Uncertain	0.98
DEOGEN2	Benign	0.095	T;T;T;T
Eigen	Benign	0.015
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.75	D
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.14	T;T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.84	L;L;L;L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.1	N;.;.;.
REVEL	Benign	0.18
Sift	Benign	0.050	D;.;.;.
Sift4G	Benign	0.22	T;.;.;.
Polyphen		0.016	B;B;B;B
Vest4		0.051
MutPred		0.54		Gain of phosphorylation at N240 (P = 0.006);Gain of phosphorylation at N240 (P = 0.006);Gain of phosphorylation at N240 (P = 0.006);Gain of phosphorylation at N240 (P = 0.006);
MVP		0.75
MPC		0.86
ClinPred		0.68	D
GERP RS		5.3
Varity_R		0.050
gMVP		0.67

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: chr1-101705259;