Variant 16-28983283-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_032038.3(SPNS1):c.1313T>C(p.Ile438Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,613,762 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

SPNS1
NM_032038.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.63

Variant links:

Genes affected

SPNS1 (HGNC:30621): (SPNS lysolipid transporter 1, lysophospholipid) Predicted to enable transmembrane transporter activity. Predicted to be involved in lipid transport and transmembrane transport. Located in lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

SPNS1 links:

ENSG00000261067 (HGNC:):

ENSG00000261067 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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/exons	MANE	Protein	UniProt
SPNS1	NM_032038.3 linkuse as main transcript	c.1313T>C	p.Ile438Thr	missense_variant	10/12	ENST00000311008.16	NP_114427.1	Q9H2V7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPNS1	ENST00000311008.16 linkuse as main transcript	c.1313T>C	p.Ile438Thr	missense_variant	10/12	1	NM_032038.3	ENSP00000309945.11		Q9H2V7-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251270

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000335

AC:

AN:

1461588

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000224

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:

0.0000405

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.00000824

AC:

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

Nov 10, 2024

The c.1313T>C (p.I438T) alteration is located in exon 10 (coding exon 10) of the SPNS1 gene. This alteration results from a T to C substitution at nucleotide position 1313, causing the isoleucine (I) at amino acid position 438 to be replaced by a threonine (T). 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

0.34

BayesDel_addAF

Uncertain

0.068

BayesDel_noAF

Uncertain

0.030

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.75

.;D;.;.;.;T

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.72

T;T;T;T;T;D

M_CAP

Benign

0.027

MetaRNN

Uncertain

0.60

D;D;D;D;D;D

MetaSVM

Benign

-0.66

MutationAssessor

Benign

1.3

.;L;.;.;.;.

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-3.7

D;D;D;D;D;D

REVEL

Uncertain

0.41

Sift

Benign

0.17

T;T;T;T;T;T

Sift4G

Benign

0.20

T;T;T;T;T;T

Polyphen

0.53, 0.20, 0.99, 0.57

.;P;B;D;P;.

Vest4

0.86

MutPred

0.50

.;Loss of stability (P = 0.0026);.;.;.;.;

MVP

0.34

MPC

0.78

ClinPred

0.88

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.21

gMVP

0.83

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