19-10514299-G-C

Variant names:

• chr19-10514299-G-C
• NM_030760.5:c.713C>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_030760.5(S1PR5):​c.713C>G​(p.Thr238Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: S1PR5 NM_030760.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.463

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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040605396).
• BP6: Variant 19-10514299-G-C is Benign according to our data. Variant chr19-10514299-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3436738.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
S1PR5	NM_030760.5	c.713C>G	p.Thr238Ser	missense_variant	Exon 2 of 2	ENST00000333430.6	NP_110387.1
S1PR5	NM_001166215.2	c.713C>G	p.Thr238Ser	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.713C>G	p.Thr238Ser	missense_variant	Exon 2 of 2	1	NM_030760.5	ENSP00000328472.3
S1PR5	ENST00000439028.3	c.713C>G	p.Thr238Ser	missense_variant	Exon 2 of 2	2		ENSP00000416915.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jul 09, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.041
DANN	Benign	0.45
DEOGEN2	Benign	0.019	T;T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.19	.;T;T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.041	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.2	N;.;N
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.21	N;.;N
REVEL	Benign	0.0070
Sift	Benign	0.49	T;.;T
Sift4G	Benign	0.51	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.051
MutPred		0.37		Loss of loop (P = 0.0288);.;Loss of loop (P = 0.0288);
MVP		0.23
ClinPred		0.034	T
GERP RS		-8.8
Varity_R		0.041
gMVP		0.099

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: chr19-10624975;