NM_182538.5:c.1498G>A

Variant names:

• chr17-4487853-G-A
• NM_182538.5:c.1498G>A

Variant summary

Our verdict is Likely benign. The variant received -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. 16/22 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
• Publications: 0 publications found

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]

SPNS2-AS1 (HGNC:55787): (SPNS2 antisense RNA 1)

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=0.024877608).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182538.5. 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
	SPNS3	NM_182538.5	MANE Select	c.1498G>A	p.Gly500Ser	missense	Exon 12 of 12	NP_872344.3
	SPNS3	NM_001320449.2		c.1117G>A	p.Gly373Ser	missense	Exon 11 of 11	NP_001307378.1	Q6ZMD2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPNS3	ENST00000355530.7	TSL:2 MANE Select	c.1498G>A	p.Gly500Ser	missense	Exon 12 of 12	ENSP00000347721.2	Q6ZMD2-1
	SPNS3	ENST00000575194.5	TSL:1	n.*752G>A		non_coding_transcript_exon	Exon 11 of 11	ENSP00000460781.1	I3L3W7
	SPNS3	ENST00000575194.5	TSL:1	n.*752G>A		3_prime_UTR	Exon 11 of 11	ENSP00000460781.1	I3L3W7

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		-1.6
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

Other links and lift over

hg19: chr17-4391148;