17-4487886-GAG-AAA

Variant names:

• chr17-4487886-GAG-AAA
• NM_182538.5:c.1531_1533delGAGinsAAA
• SPNS3 p.Glu511Lys

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_182538.5(SPNS3):​c.1531_1533delGAGinsAAA​(p.Glu511Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: SPNS3 NM_182538.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.146
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.1531_1533delGAGinsAAA	p.Glu511Lys	missense	N/A	NP_872344.3
	SPNS3	NM_001320449.2		c.1150_1152delGAGinsAAA	p.Glu384Lys	missense	N/A	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.1531_1533delGAGinsAAA	p.Glu511Lys	missense	N/A	ENSP00000347721.2	Q6ZMD2-1
	SPNS3	ENST00000575194.5	TSL:1	n.*785_*787delGAGinsAAA		non_coding_transcript_exon	Exon 11 of 11	ENSP00000460781.1	I3L3W7
	SPNS3	ENST00000575194.5	TSL:1	n.*785_*787delGAGinsAAA		3_prime_UTR	Exon 11 of 11	ENSP00000460781.1	I3L3W7

Frequencies

GnomAD3 genomes Cov.: 34

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.15

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-4391181;