dbSNP rs138065168: S1PR3:p.Arg321Gln (chr9-89002162-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005226.4(S1PR3):c.962G>A(p.Arg321Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 1,613,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

S1PR3
NM_005226.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.981

Variant links:

Genes affected

S1PR3 (HGNC:3167): (sphingosine-1-phosphate receptor 3) This gene encodes a member of the EDG family of receptors, which are G protein-coupled receptors. This protein has been identified as a functional receptor for sphingosine 1-phosphate and likely contributes to the regulation of angiogenesis and vascular endothelial cell function. [provided by RefSeq, Jul 2008]

S1PR3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.007769704).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
S1PR3	NM_005226.4 link	c.962G>A	p.Arg321Gln	missense_variant	Exon 2 of 2	ENST00000358157.3	NP_005217.2	Q99500
S1PR3	NM_001395848.1 link	c.962G>A	p.Arg321Gln	missense_variant	Exon 3 of 3		NP_001382777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
S1PR3	ENST00000358157.3 link	c.962G>A	p.Arg321Gln	missense_variant	Exon 2 of 2	1	NM_005226.4	ENSP00000350878.2		Q99500
S1PR3	ENST00000375846.3 link	c.962G>A	p.Arg321Gln	missense_variant	Exon 1 of 1	6		ENSP00000365006.3		Q99500

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152016

Hom.:

Cov.:

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:

0.000971

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000559

AC:

AN:

250550

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

135498

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000761

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000233

AC:

AN:

1461588

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

727098

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000756

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152134

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000779

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000491

ExAC

AF:

0.0000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.021

DANN

Benign

0.86

DEOGEN2

Benign

0.074

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.52

.;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.0078

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;L

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.040

N;N

REVEL

Benign

0.010

Sift

Benign

0.35

T;T

Sift4G

Benign

0.66

T;T

Polyphen

0.0030

B;B

Vest4

0.053

MVP

0.21

MPC

0.52

ClinPred

0.035

GERP RS

-3.0

Varity_R

0.011

gMVP

0.24

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