rs769745882

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-10513939-C-G
• chr19-10513939-C-T

Variant summary

Our verdict is Likely benign. Variant got -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. 16/20 in silico tools predict a benign 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: 0.0000014 (0 hom.)
• Consequence: S1PR5 NM_030760.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.551

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

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
S1PR5	NM_030760.5	c.1073G>C	p.Gly358Ala	missense_variant	Exon 2 of 2	ENST00000333430.6	NP_110387.1
S1PR5	NM_001166215.2	c.1073G>C	p.Gly358Ala	missense_variant	Exon 2 of 2		NP_001159687.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
S1PR5	ENST00000333430.6	c.1073G>C	p.Gly358Ala	missense_variant	Exon 2 of 2	1	NM_030760.5	ENSP00000328472.3
S1PR5	ENST00000439028.3	c.1073G>C	p.Gly358Ala	missense_variant	Exon 2 of 2	2		ENSP00000416915.2

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

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

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	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;T;T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.46	.;T;T
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.052	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.81	L;.;L
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.080	N;.;N
REVEL	Benign	0.12
Sift	Benign	0.70	T;.;T
Sift4G	Benign	0.65	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.082
MutPred		0.15		Loss of catalytic residue at P354 (P = 0.1146);.;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

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: chr19-10624615;