Variant 17-4446141-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_182538.5(SPNS3):c.496G>A(p.Val166Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000454 in 1,613,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00046 ( 0 hom. )

Consequence

SPNS3
NM_182538.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.52

Variant links:

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 links:

SPNS3 (HGNC:):

SPNS3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14046982).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPNS3	NM_182538.5 linkuse as main transcript	c.496G>A	p.Val166Met	missense_variant	4/12	ENST00000355530.7	NP_872344.3	Q6ZMD2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SPNS3	ENST00000355530.7 linkuse as main transcript	c.496G>A	p.Val166Met	missense_variant	4/12	2	NM_182538.5	ENSP00000347721.2	Q6ZMD2-1
SPNS3	ENST00000575194.5 linkuse as main transcript	n.359G>A		non_coding_transcript_exon_variant	3/11	1		ENSP00000460781.1	I3L3W7
SPNS3	ENST00000572078.1 linkuse as main transcript	n.287G>A		non_coding_transcript_exon_variant	2/4	3
SPNS3	ENST00000576069.5 linkuse as main transcript	n.370G>A		non_coding_transcript_exon_variant	3/6	5		ENSP00000519557.1

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000618

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000334

AC:

AN:

251142

Hom.:

AF XY:

0.000280

AC XY:

AN XY:

135726

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000637

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000484

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000461

AC:

673

AN:

1461426

Hom.:

Cov.:

AF XY:

0.000421

AC XY:

306

AN XY:

726988

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000537

Gnomad4 ASJ exome

AF:

0.0000766

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000562

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.000388

AC:

AN:

152112

Hom.:

Cov.:

AF XY:

0.000350

AC XY:

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.000720

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000618

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000679

Hom.:

Bravo

AF:

0.000468

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000321

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2021

The c.496G>A (p.V166M) alteration is located in exon 4 (coding exon 4) of the SPNS3 gene. This alteration results from a G to A substitution at nucleotide position 496, causing the valine (V) at amino acid position 166 to be replaced by a methionine (M). 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

Benign

0.15

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.16

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.012

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.7

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.6

REVEL

Benign

0.14

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.015

Polyphen

0.99

Vest4

0.33

MVP

0.29

MPC

0.29

ClinPred

0.035

GERP RS

1.6

Varity_R

0.21

gMVP

0.47

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over