17-4446159-C-A

Variant names:

• chr17-4446159-C-A
• NM_182538.5:c.514C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_182538.5(SPNS3):​c.514C>A​(p.Arg172Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,928 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SPNS3 NM_182538.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.457

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPNS3	NM_182538.5	c.514C>A	p.Arg172Ser	missense_variant	Exon 4 of 12	ENST00000355530.7	NP_872344.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPNS3	ENST00000355530.7	c.514C>A	p.Arg172Ser	missense_variant	Exon 4 of 12	2	NM_182538.5	ENSP00000347721.2
SPNS3	ENST00000575194.5	n.377C>A		non_coding_transcript_exon_variant	Exon 3 of 11	1		ENSP00000460781.1
SPNS3	ENST00000572078.1	n.305C>A		non_coding_transcript_exon_variant	Exon 2 of 4	3
SPNS3	ENST00000576069.5	n.388C>A		non_coding_transcript_exon_variant	Exon 3 of 6	5		ENSP00000519557.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1460928 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726658

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	3.6
DANN	Uncertain	0.97
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.17
Sift	Benign	0.31	T
Sift4G	Benign	0.42	T
Polyphen		0.34	B
Vest4		0.57
MutPred		0.69		Loss of methylation at R172 (P = 0.0116);
MVP		0.26
MPC		0.29
ClinPred		0.17	T
GERP RS		0.22
Varity_R		0.23
gMVP		0.56

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: chr17-4349454;