dbSNP rs1243463923: S1PR5:p.Arg229Gln (chr19-10514326-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030760.5(S1PR5):c.686G>A(p.Arg229Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000283 in 1,415,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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: 0.0000028 ( 0 hom. )

Consequence

S1PR5
NM_030760.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.243

Publications

0 publications found

Variant links:

Genes affected

S1PR5 (HGNC:14299): (sphingosine-1-phosphate receptor 5) The lysosphingolipid sphingosine 1-phosphate (S1P) regulates cell proliferation, apoptosis, motility, and neurite retraction. Its actions may be both intracellular as a second messenger and extracellular as a receptor ligand. S1P and the structurally related lysolipid mediator lysophosphatidic acid (LPA) signal cells through a set of G protein-coupled receptors known as EDG receptors. Some EDG receptors (e.g., EDG1; MIM 601974) are S1P receptors; others (e.g., EDG2; MIM 602282) are LPA receptors.[supplied by OMIM, Mar 2008]

S1PR5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11417964).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030760.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S1PR5	NM_030760.5	MANE Select	c.686G>A	p.Arg229Gln	missense	Exon 2 of 2	NP_110387.1	Q9H228-1
	S1PR5	NM_001166215.2		c.686G>A	p.Arg229Gln	missense	Exon 2 of 2	NP_001159687.1	Q9H228-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S1PR5	ENST00000333430.6	TSL:1 MANE Select	c.686G>A	p.Arg229Gln	missense	Exon 2 of 2	ENSP00000328472.3	Q9H228-1
	S1PR5	ENST00000439028.3	TSL:2	c.686G>A	p.Arg229Gln	missense	Exon 2 of 2	ENSP00000416915.2	Q9H228-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000118

AC:

AN:

169048

AF XY:

0.0000218

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000117

Gnomad EAS exome

AF:

0.0000797

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000283

AC:

AN:

1415856

Hom.:

Cov.:

AF XY:

0.00000429

AC XY:

AN XY:

700110

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32490

American (AMR)

AF:

0.00

AC:

AN:

36548

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25306

East Asian (EAS)

AF:

0.0000538

AC:

AN:

37192

South Asian (SAS)

AF:

0.00

AC:

AN:

81456

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48848

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5680

European-Non Finnish (NFE)

AF:

0.00000184

AC:

AN:

1089606

Other (OTH)

AF:

0.00

AC:

AN:

58730

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.064

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.40

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.13

PhyloP100

-0.24

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.7

REVEL

Benign

0.069

Sift

Uncertain

0.029

Sift4G

Benign

0.43

Polyphen

0.54

Vest4

0.057

MutPred

0.44

Loss of MoRF binding (P = 0.0185)

MVP

0.64

ClinPred

0.064

GERP RS

-2.3

Varity_R

0.10

gMVP

0.25

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over