9-89001238-G-T

Variant names:

• chr9-89001238-G-T
• rs201961912
• NM_005226.4:c.38G>T

Variant summary

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

The NM_005226.4(S1PR3):​c.38G>T​(p.Arg13Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000973 in 1,613,834 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R13P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00034 (1 hom., cov: 33)
  • Exomes 𝑓: 0.000072 (0 hom.)
• Consequence: S1PR3 NM_005226.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.434
• Publications: 0 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0062089264).

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.38G>T	p.Arg13Leu	missense	Exon 2 of 2	NP_005217.2
	S1PR3	NM_001395848.1		c.38G>T	p.Arg13Leu	missense	Exon 3 of 3	NP_001382777.1	Q99500

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S1PR3	ENST00000358157.3	TSL:1 MANE Select	c.38G>T	p.Arg13Leu	missense	Exon 2 of 2	ENSP00000350878.2	Q99500
	S1PR3	ENST00000375846.3	TSL:6	c.38G>T	p.Arg13Leu	missense	Exon 1 of 1	ENSP00000365006.3	Q99500
	S1PR3	ENST00000887789.1		c.38G>T	p.Arg13Leu	missense	Exon 3 of 3	ENSP00000557848.1

Frequencies

GnomAD3 genomes AF: 0.000342 AC: 52 AN: 152166 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000893

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

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: 0.0000441

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000143 AC: 36 AN: 251128 AF XY: 0.000110

Gnomad AFR exome AF: 0.00105

Gnomad AMR exome AF: 0.000463

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000718 AC: 105 AN: 1461550 Hom.: 0 Cov.: 30 AF XY: 0.0000743 AC XY: 54 AN XY: 727018

African (AFR) AF: 0.000329 AC: 11 AN: 33474

American (AMR) AF: 0.000425 AC: 19 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.0000522 AC: 58 AN: 1111774

Other (OTH) AF: 0.000282 AC: 17 AN: 60386

GnomAD4 genome AF: 0.000341 AC: 52 AN: 152284 Hom.: 1 Cov.: 33 AF XY: 0.000269 AC XY: 20 AN XY: 74468

African (AFR) AF: 0.000890 AC: 37 AN: 41562

American (AMR) AF: 0.000719 AC: 11 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68012

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.0000447 Hom.: 0

Bravo AF: 0.000329

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000148 AC: 18

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.59
DANN	Benign	0.74
DEOGEN2	Benign	0.040	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.0062	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N
PhyloP100		-0.43
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.11	N
REVEL	Benign	0.10
Sift	Benign	0.74	T
Sift4G	Benign	0.77	T
Polyphen		0.0	B
Vest4		0.043
MVP		0.22
MPC		0.56
ClinPred		0.0053	T
GERP RS		-5.2
Varity_R		0.043
gMVP		0.43

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

Other links and lift over

dbSNP: rs201961912; hg19: chr9-91616153;