NM_030760.5:c.1073G>C

Variant names:

• chr19-10513939-C-G
• rs769745882
• NM_030760.5:c.1073G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_030760.5(S1PR5):​c.1073G>C​(p.Gly358Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,450,572 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G358E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: S1PR5 NM_030760.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.551
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052492082).

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.1073G>C	p.Gly358Ala	missense	Exon 2 of 2	NP_110387.1	Q9H228-1
	S1PR5	NM_001166215.2		c.1073G>C	p.Gly358Ala	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.1073G>C	p.Gly358Ala	missense	Exon 2 of 2	ENSP00000328472.3	Q9H228-1
	S1PR5	ENST00000439028.3	TSL:2	c.1073G>C	p.Gly358Ala	missense	Exon 2 of 2	ENSP00000416915.2	Q9H228-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1450572 Hom.: 0 Cov.: 29 AF XY: 0.00000139 AC XY: 1 AN XY: 721014

African (AFR) AF: 0.00 AC: 0 AN: 32992

American (AMR) AF: 0.00 AC: 0 AN: 43082

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25752

East Asian (EAS) AF: 0.00 AC: 0 AN: 39412

South Asian (SAS) AF: 0.00 AC: 0 AN: 85518

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4978

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1107716

Other (OTH) AF: 0.00 AC: 0 AN: 59726

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	11
DANN	Benign	0.55
DEOGEN2	Benign	0.064	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.55
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.12
Sift	Benign	0.70	T
Sift4G	Benign	0.65	T
Polyphen		0.0	B
Vest4		0.082
MutPred		0.15		Loss of catalytic residue at P354 (P = 0.1146)
MVP		0.69
ClinPred		0.055	T
GERP RS		2.7
Varity_R		0.10
gMVP		0.22
Mutation Taster		=93/7	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: rs769745882; hg19: chr19-10624615;