rs1553405319

Variant summary

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

The ENST00000638572.2(ST3GAL5):​c.479C>T​(p.Pro160Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P160H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

ST3GAL5
ENST00000638572.2 missense

Scores

2
8
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.84
Variant links:
Genes affected
ST3GAL5 (HGNC:10872): (ST3 beta-galactoside alpha-2,3-sialyltransferase 5) Ganglioside GM3 is known to participate in the induction of cell differentiation, modulation of cell proliferation, maintenance of fibroblast morphology, signal transduction, and integrin-mediated cell adhesion. The protein encoded by this gene is a type II membrane protein which catalyzes the formation of GM3 using lactosylceramide as the substrate. The encoded protein is a member of glycosyltransferase family 29 and may be localized to the Golgi apparatus. Mutation in this gene has been associated with Amish infantile epilepsy syndrome. Transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

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
ST3GAL5NM_003896.4 linkuse as main transcriptc.479C>T p.Pro160Leu missense_variant 4/7 ENST00000638572.2 NP_003887.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ST3GAL5ENST00000638572.2 linkuse as main transcriptc.479C>T p.Pro160Leu missense_variant 4/71 NM_003896.4 ENSP00000491316 A1Q9UNP4-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

GM3 synthase deficiency Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJun 22, 2020Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals with ST3GAL5-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with leucine at codon 160 of the ST3GAL5 protein (p.Pro160Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.25
BayesDel_addAF
Uncertain
0.064
T
BayesDel_noAF
Benign
-0.15
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.48
T;.;.;.;.;.;.;.;.;.;T;.;T
Eigen
Uncertain
0.37
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.97
D;D;.;.;D;D;D;.;.;.;D;D;D
M_CAP
Benign
0.038
D
MetaRNN
Uncertain
0.68
D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.65
T
MutationAssessor
Benign
0.91
L;.;.;.;.;.;.;.;.;.;.;.;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.48
T
PROVEAN
Pathogenic
-6.5
.;D;D;.;.;.;.;.;.;.;.;.;D
REVEL
Benign
0.24
Sift
Benign
0.055
.;T;T;.;.;.;.;.;.;.;.;.;D
Sift4G
Benign
0.49
.;T;T;.;.;.;.;.;.;.;.;.;.
Polyphen
0.88
P;D;D;D;.;.;.;D;D;D;.;D;.
Vest4
0.45, 0.46
MutPred
0.74
Loss of disorder (P = 0.0268);.;.;.;.;Loss of disorder (P = 0.0268);.;.;.;.;.;.;.;
MVP
0.71
MPC
1.0
ClinPred
0.97
D
GERP RS
5.1
Varity_R
0.28
gMVP
0.82

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs1553405319; hg19: chr2-86075167; COSMIC: COSV60384986; COSMIC: COSV60384986; API