19-10514391-A-G

Variant names:

• chr19-10514391-A-G
• rs6511701
• NM_030760.5:c.621T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_030760.5(S1PR5):​c.621T>C​(p.Ala207Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,450,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 35)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: S1PR5 NM_030760.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93
• Publications: 24 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=1.93 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
S1PR5	NM_030760.5	c.621T>C	p.Ala207Ala	synonymous_variant	Exon 2 of 2	ENST00000333430.6	NP_110387.1
S1PR5	NM_001166215.2	c.621T>C	p.Ala207Ala	synonymous_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.621T>C	p.Ala207Ala	synonymous_variant	Exon 2 of 2	1	NM_030760.5	ENSP00000328472.3
S1PR5	ENST00000439028.3	c.621T>C	p.Ala207Ala	synonymous_variant	Exon 2 of 2	2		ENSP00000416915.2

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1450718 Hom.: 0 Cov.: 82 AF XY: 0.00 AC XY: 0 AN XY: 720718

African (AFR) AF: 0.00 AC: 0 AN: 33316

American (AMR) AF: 0.00 AC: 0 AN: 42878

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25894

East Asian (EAS) AF: 0.00 AC: 0 AN: 39202

South Asian (SAS) AF: 0.00 AC: 0 AN: 84642

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107552

Other (OTH) AF: 0.00 AC: 0 AN: 59930

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.8
DANN	Benign	0.19
PhyloP100		1.9

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: rs6511701; hg19: chr19-10625067;