rs1553405319
Positions:
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
ENST00000638572.2 missense
Scores
2
8
9
Clinical Significance
Conservation
PhyloP100: 6.84
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]
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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 |
---|---|---|---|---|---|---|---|---|
ST3GAL5 | NM_003896.4 | c.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 |
---|---|---|---|---|---|---|---|---|---|---|
ST3GAL5 | ENST00000638572.2 | c.479C>T | p.Pro160Leu | missense_variant | 4/7 | 1 | NM_003896.4 | ENSP00000491316 | A1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 32
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 submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 22, 2020 | Algorithms 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
T;.;.;.;.;.;.;.;.;.;T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;.;.;D;D;D;.;.;.;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.;.;.;.;.;.;.;.;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
.;D;D;.;.;.;.;.;.;.;.;.;D
REVEL
Benign
Sift
Benign
.;T;T;.;.;.;.;.;.;.;.;.;D
Sift4G
Benign
.;T;T;.;.;.;.;.;.;.;.;.;.
Polyphen
P;D;D;D;.;.;.;D;D;D;.;D;.
Vest4
0.45, 0.46
MutPred
Loss of disorder (P = 0.0268);.;.;.;.;Loss of disorder (P = 0.0268);.;.;.;.;.;.;.;
MVP
0.71
MPC
1.0
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at