19-10514338-C-T

Variant names:

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

Variant summary

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

The NM_030760.5(S1PR5):​c.674G>A​(p.Arg225His) variant causes a missense change. The variant allele was found at a frequency of 0.000000709 in 1,410,222 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R225L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: S1PR5 NM_030760.5 missense
• Clinical Significance: Not reported in ClinVar
• 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>A	p.Arg225His	missense	Exon 2 of 2	NP_110387.1	Q9H228-1
	S1PR5	NM_001166215.2		c.674G>A	p.Arg225His	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>A	p.Arg225His	missense	Exon 2 of 2	ENSP00000328472.3	Q9H228-1
	S1PR5	ENST00000439028.3	TSL:2	c.674G>A	p.Arg225His	missense	Exon 2 of 2	ENSP00000416915.2	Q9H228-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.09e-7 AC: 1 AN: 1410222 Hom.: 0 Cov.: 30 AF XY: 0.00000143 AC XY: 1 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: 0.00 AC: 0 AN: 1087630

Other (OTH) AF: 0.0000171 AC: 1 AN: 58512

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Benign	0.085
Eigen_PC	Benign	-0.053
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.57	T
M_CAP	Pathogenic	0.42	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.52	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		4.2
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.32
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.15
MutPred		0.51		Loss of MoRF binding (P = 0.0092)
MVP		0.94
ClinPred		0.95	D
GERP RS		1.6
Varity_R		0.25
gMVP		0.42
Mutation Taster		=85/15	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;