19-10514338-C-A

Variant names:

• chr19-10514338-C-A
• rs201726285
• NM_030760.5:c.674G>T

Variant summary

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

The NM_030760.5(S1PR5):​c.674G>T​(p.Arg225Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000284 in 1,410,222 control chromosomes in the GnomAD database, with no homozygous occurrence. 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.17
• Publications: 0 publications found

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]

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_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.674G>T	p.Arg225Leu	missense	Exon 2 of 2	NP_110387.1	Q9H228-1
	S1PR5	NM_001166215.2		c.674G>T	p.Arg225Leu	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.674G>T	p.Arg225Leu	missense	Exon 2 of 2	ENSP00000328472.3	Q9H228-1
	S1PR5	ENST00000439028.3	TSL:2	c.674G>T	p.Arg225Leu	missense	Exon 2 of 2	ENSP00000416915.2	Q9H228-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000284 AC: 4 AN: 1410222 Hom.: 0 Cov.: 30 AF XY: 0.00000574 AC XY: 4 AN XY: 697008

African (AFR) AF: 0.00 AC: 0 AN: 32064

American (AMR) AF: 0.00 AC: 0 AN: 36122

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25218

East Asian (EAS) AF: 0.00 AC: 0 AN: 36484

South Asian (SAS) AF: 0.00 AC: 0 AN: 80672

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48016

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5504

European-Non Finnish (NFE) AF: 0.00000368 AC: 4 AN: 1087630

Other (OTH) AF: 0.00 AC: 0 AN: 58512

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T
Eigen	Benign	0.046
Eigen_PC	Benign	-0.081
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.54	T
M_CAP	Pathogenic	0.35	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.40	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		4.2
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.012	D
Polyphen		0.94	P
Vest4		0.35
MutPred		0.54		Loss of MoRF binding (P = 0.0062)
MVP		0.89
ClinPred		0.97	D
GERP RS		1.6
Varity_R		0.47
gMVP		0.66
Mutation Taster		=75/25	polymorphism

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: rs201726285; hg19: chr19-10625014;