chr17-4445085-C-G

Position:

• chr17-4445085-C-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_182538.5(SPNS3):​c.319C>G​(p.Arg107Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPNS3 NM_182538.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.77

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_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.978

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPNS3	NM_182538.5	c.319C>G	p.Arg107Gly	missense_variant	3/12	ENST00000355530.7	NP_872344.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPNS3	ENST00000355530.7	c.319C>G	p.Arg107Gly	missense_variant	3/12	2	NM_182538.5	ENSP00000347721.2
SPNS3	ENST00000575194.5	n.266-963C>G		intron_variant		1		ENSP00000460781.1
SPNS3	ENST00000572078.1	n.110C>G		non_coding_transcript_exon_variant	1/4	3
SPNS3	ENST00000576069.5	n.277-963C>G		intron_variant		5		ENSP00000519557.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Nov 21, 2024

The c.319C>G (p.R107G) alteration is located in exon 3 (coding exon 3) of the SPNS3 gene. This alteration results from a C to G substitution at nucleotide position 319, causing the arginine (R) at amino acid position 107 to be replaced by a glycine (G). 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	Pathogenic	0.61
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.65	D
Eigen	Pathogenic	0.68
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Uncertain	0.25	D
MutationAssessor	Pathogenic	3.3	M
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-6.8	D
REVEL	Pathogenic	0.78
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.94
MutPred		0.80		Loss of methylation at R107 (P = 0.0294);
MVP		0.60
MPC		0.67
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.91
gMVP		0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr17-4348380;