17-4487868-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_182538.5(SPNS3):​c.1513G>A​(p.Ala505Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000378 in 1,614,046 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

SPNS3
NM_182538.5 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.645
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.019054592).
BP6
Variant 17-4487868-G-A is Benign according to our data. Variant chr17-4487868-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3448670.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPNS3NM_182538.5 linkc.1513G>A p.Ala505Thr missense_variant Exon 12 of 12 ENST00000355530.7 NP_872344.3 Q6ZMD2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPNS3ENST00000355530.7 linkc.1513G>A p.Ala505Thr missense_variant Exon 12 of 12 2 NM_182538.5 ENSP00000347721.2 Q6ZMD2-1
SPNS3ENST00000575194.5 linkn.*767G>A non_coding_transcript_exon_variant Exon 11 of 11 1 ENSP00000460781.1 I3L3W7
SPNS3ENST00000575194.5 linkn.*767G>A 3_prime_UTR_variant Exon 11 of 11 1 ENSP00000460781.1 I3L3W7
SPNS3ENST00000575796.1 linkn.*6G>A downstream_gene_variant 5

Frequencies

GnomAD3 genomes
AF:
0.0000328
AC:
5
AN:
152272
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000964
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251228
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135826
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000383
AC:
56
AN:
1461656
Hom.:
0
Cov.:
33
AF XY:
0.0000385
AC XY:
28
AN XY:
727134
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000441
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152390
Hom.:
0
Cov.:
34
AF XY:
0.0000268
AC XY:
2
AN XY:
74526
show subpopulations
Gnomad4 AFR
AF:
0.0000962
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000564
Hom.:
0
Bravo
AF:
0.0000340
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Aug 20, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.062
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.85
CADD
Benign
0.026
DANN
Benign
0.59
DEOGEN2
Benign
0.0032
T
Eigen
Benign
-2.2
Eigen_PC
Benign
-2.2
FATHMM_MKL
Benign
0.0034
N
LIST_S2
Benign
0.28
T
M_CAP
Benign
0.0032
T
MetaRNN
Benign
0.019
T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
-1.4
N
PrimateAI
Benign
0.25
T
PROVEAN
Benign
0.36
N
REVEL
Benign
0.039
Sift
Benign
0.81
T
Sift4G
Benign
0.90
T
Polyphen
0.0020
B
Vest4
0.022
MVP
0.014
MPC
0.12
ClinPred
0.033
T
GERP RS
-7.8
Varity_R
0.027
gMVP
0.17

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.

Other links and lift over

dbSNP: rs201626302; hg19: chr17-4391163; API