NM_182538.5:c.95T>C

Variant names:

• chr17-4434062-T-C
• NM_182538.5:c.95T>C

Variant summary

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

The NM_182538.5(SPNS3):​c.95T>C​(p.Ile32Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 6.9e-7 (0 hom.)
• Consequence: SPNS3 NM_182538.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.809

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 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=0.043555766).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPNS3	NM_182538.5	c.95T>C	p.Ile32Thr	missense_variant	Exon 1 of 12	ENST00000355530.7	NP_872344.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPNS3	ENST00000355530.7	c.95T>C	p.Ile32Thr	missense_variant	Exon 1 of 12	2	NM_182538.5	ENSP00000347721.2
SPNS3	ENST00000575194.5	n.95T>C		non_coding_transcript_exon_variant	Exon 1 of 11	1		ENSP00000460781.1
SPNS3	ENST00000576069.5	n.106T>C		non_coding_transcript_exon_variant	Exon 1 of 6	5		ENSP00000519557.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458722 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 725640

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	0.065
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.026
DANN	Benign	0.23
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0039	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.015
Sift	Benign	0.62	T
Sift4G	Benign	0.60	T
Polyphen		0.0	B
Vest4		0.019
MutPred		0.36		Gain of glycosylation at I32 (P = 0);
MVP		0.030
MPC		0.16
ClinPred		0.078	T
GERP RS		-0.40
Varity_R		0.032
gMVP		0.10

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: chr17-4337357;