Variant 17-4445094-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_182538.5(SPNS3):c.328C>T(p.Arg110Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 1,614,140 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 21 hom. )

Consequence

SPNS3
NM_182538.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.66

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.070468366).

BP6

Variant 17-4445094-C-T is Benign according to our data. Variant chr17-4445094-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2647254.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPNS3	NM_182538.5 linkuse as main transcript	c.328C>T	p.Arg110Cys	missense_variant	3/12	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.328C>T	p.Arg110Cys	missense_variant	3/12	2	NM_182538.5	ENSP00000347721.2	Q6ZMD2-1
SPNS3	ENST00000575194.5 linkuse as main transcript	n.266-954C>T		intron_variant		1		ENSP00000460781.1	I3L3W7
SPNS3	ENST00000572078.1 linkuse as main transcript	n.119C>T		non_coding_transcript_exon_variant	1/4	3
SPNS3	ENST00000576069.5 linkuse as main transcript	n.277-954C>T		intron_variant		5		ENSP00000519557.1

Frequencies

GnomAD3 genomes

AF:

0.00142

AC:

216

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00849

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00190

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00215

AC:

540

AN:

251436

Hom.:

AF XY:

0.00272

AC XY:

369

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000636

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00986

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00163

Gnomad OTH exome

AF:

0.00424

GnomAD4 exome

AF:

0.00190

AC:

2777

AN:

1461834

Hom.:

Cov.:

AF XY:

0.00217

AC XY:

1581

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000738

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0105

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00150

Gnomad4 OTH exome

AF:

0.00169

GnomAD4 genome

AF:

0.00141

AC:

214

AN:

152306

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

107

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00190

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00172

Hom.:

Bravo

AF:

0.00119

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00221

AC:

ExAC

AF:

0.00243

AC:

295

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.00256

EpiControl

AF:

0.00154

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

SPNS3: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.0045

BayesDel_noAF

Pathogenic

0.23

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.56

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.94

MetaRNN

Benign

0.070

MetaSVM

Uncertain

0.20

MutationAssessor

Pathogenic

3.3

PrimateAI

Uncertain

0.60

PROVEAN

Pathogenic

-7.8

REVEL

Uncertain

0.61

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.97

MVP

0.57

MPC

0.69

ClinPred

0.16

GERP RS

4.5

Varity_R

0.83

gMVP

0.84

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