Genetic Variant NM_005226.4:c.964G>A (chr9-89002164-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005226.4(S1PR3):c.964G>A(p.Gly322Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 1,613,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

S1PR3
NM_005226.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.55

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06420365).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005226.4. 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
	S1PR3	NM_005226.4	MANE Select	c.964G>A	p.Gly322Arg	missense	Exon 2 of 2	NP_005217.2
	S1PR3	NM_001395848.1		c.964G>A	p.Gly322Arg	missense	Exon 3 of 3	NP_001382777.1	Q99500

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
S1PR3	ENST00000358157.3	TSL:1 MANE Select	c.964G>A	p.Gly322Arg	missense	Exon 2 of 2	ENSP00000350878.2	Q99500
S1PR3	ENST00000375846.3	TSL:6	c.964G>A	p.Gly322Arg	missense	Exon 1 of 1	ENSP00000365006.3	Q99500
S1PR3	ENST00000887789.1		c.964G>A	p.Gly322Arg	missense	Exon 3 of 3	ENSP00000557848.1

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000604

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000638

AC:

AN:

250818

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.000803

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.0000123

AC:

AN:

1461748

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727184

show subpopulations

African (AFR)

AF:

0.000448

AC:

AN:

33480

American (AMR)

AF:

0.0000447

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53278

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112012

Other (OTH)

AF:

0.0000166

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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

AF:

0.000164

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.000602

AC:

AN:

41510

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5140

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000387

Hom.:

Bravo

AF:

0.000144

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000824

AC:

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

0.13

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Benign

0.15

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.73

M_CAP

Benign

0.0097

MetaRNN

Benign

0.064

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

PhyloP100

2.6

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.8

REVEL

Benign

0.17

Sift

Benign

0.056

Sift4G

Benign

0.094

Polyphen

0.93

Vest4

0.063

MutPred

0.39

Gain of MoRF binding (P = 0.0123)

MVP

0.62

MPC

0.66

ClinPred

0.054

GERP RS

4.2

Varity_R

0.044

gMVP

0.52

Mutation Taster

=86/14

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over