9-89001904-C-A

Variant names:

• chr9-89001904-C-A
• rs376050822
• NM_005226.4:c.704C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005226.4(S1PR3):​c.704C>A​(p.Ser235*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: S1PR3 NM_005226.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.83
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.704C>A	p.Ser235*	stop_gained	Exon 2 of 2	NP_005217.2
	S1PR3	NM_001395848.1		c.704C>A	p.Ser235*	stop_gained	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.704C>A	p.Ser235*	stop_gained	Exon 2 of 2	ENSP00000350878.2	Q99500
	S1PR3	ENST00000375846.3	TSL:6	c.704C>A	p.Ser235*	stop_gained	Exon 1 of 1	ENSP00000365006.3	Q99500
	S1PR3	ENST00000887789.1		c.704C>A	p.Ser235*	stop_gained	Exon 3 of 3	ENSP00000557848.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.54	D
BayesDel_noAF	Pathogenic	0.54
CADD	Pathogenic	36
DANN	Uncertain	1.0
Eigen	Pathogenic	0.72
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.91	D
PhyloP100		4.8
Vest4		0.92
GERP RS		4.2
Mutation Taster		=32/168	disease causing

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: rs376050822; hg19: chr9-91616819; COSMIC: COSV108882025; COSMIC: COSV108882025;