17-4487853-G-A

Position:

• chr17-4487853-G-A

Variant summary

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

The NM_182538.5(SPNS3):​c.1498G>A​(p.Gly500Ser) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: SPNS3 NM_182538.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.58

Genes affected

SPNS3 (HGNC:28433): (SPNS lysolipid transporter 3, sphingosine-1-phosphate (putative)) Predicted to enable transmembrane transporter activity. Predicted to be involved in lipid transport and transmembrane transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SPNS3 (HGNC:):

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=0.024877608).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPNS3	NM_182538.5	c.1498G>A	p.Gly500Ser	missense_variant	12/12	ENST00000355530.7	NP_872344.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPNS3	ENST00000355530.7	c.1498G>A	p.Gly500Ser	missense_variant	12/12	2	NM_182538.5	ENSP00000347721.2
SPNS3	ENST00000575194.5	n.*752G>A		non_coding_transcript_exon_variant	11/11	1		ENSP00000460781.1
SPNS3	ENST00000575194.5	n.*752G>A		3_prime_UTR_variant	11/11	1		ENSP00000460781.1
SPNS3	ENST00000575796.1	n.522G>A		non_coding_transcript_exon_variant	4/4	5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 08, 2024

The c.1498G>A (p.G500S) alteration is located in exon 12 (coding exon 12) of the SPNS3 gene. This alteration results from a G to A substitution at nucleotide position 1498, causing the glycine (G) at amino acid position 500 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.43
DANN	Benign	0.70
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.025	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.90	L
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.012
Sift	Benign	0.28	T
Sift4G	Benign	0.56	T
Polyphen		0.0030	B
Vest4		0.060
MutPred		0.13		Gain of phosphorylation at G500 (P = 0.0132);
MVP		0.030
MPC		0.13
ClinPred		0.083	T
GERP RS		-8.0
Varity_R		0.041
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr17-4391148;