rs748848824

Variant names:

• chr9-89001657-C-G
• NM_005226.4:c.457C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-89001657-C-G
• chr9-89001657-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_005226.4(S1PR3):​c.457C>G​(p.Arg153Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: S1PR3 NM_005226.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.69

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

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.97

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
S1PR3	NM_005226.4	c.457C>G	p.Arg153Gly	missense_variant	Exon 2 of 2	ENST00000358157.3	NP_005217.2
S1PR3	NM_001395848.1	c.457C>G	p.Arg153Gly	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	c.457C>G	p.Arg153Gly	missense_variant	Exon 2 of 2	1	NM_005226.4	ENSP00000350878.2
S1PR3	ENST00000375846.3	c.457C>G	p.Arg153Gly	missense_variant	Exon 1 of 1	6		ENSP00000365006.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461878 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T;T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.80	.;T
M_CAP	Benign	0.043	D
MetaRNN	Pathogenic	0.97	D;D
MetaSVM	Benign	-0.47	T
MutationAssessor	Pathogenic	3.6	H;H
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-6.9	D;D
REVEL	Uncertain	0.48
Sift	Uncertain	0.024	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.91
MutPred		0.91		Loss of MoRF binding (P = 0.0452);Loss of MoRF binding (P = 0.0452);
MVP		0.69
MPC		0.83
ClinPred		0.99	D
GERP RS		4.4
Varity_R		0.72
gMVP		0.94

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-91616572;