rs1294093559
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_006279.5(ST3GAL3):c.805A>T(p.Ile269Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
ST3GAL3
NM_006279.5 missense
NM_006279.5 missense
Scores
1
5
13
Clinical Significance
Conservation
PhyloP100: 8.76
Genes affected
ST3GAL3 (HGNC:10866): (ST3 beta-galactoside alpha-2,3-sialyltransferase 3) The protein encoded by this gene is a type II membrane protein that catalyzes the transfer of sialic acid from CMP-sialic acid to galactose-containing substrates. The encoded protein is normally found in the Golgi apparatus but can be proteolytically processed to a soluble form. This protein is a member of glycosyltransferase family 29. Mutations in this gene have been associated with a form of autosomal recessive nonsymdromic cognitive disability as well as infantile epileptic encephalopathy. Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.383888).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ST3GAL3 | NM_006279.5 | c.805A>T | p.Ile269Phe | missense_variant | 10/12 | ENST00000347631.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ST3GAL3 | ENST00000347631.8 | c.805A>T | p.Ile269Phe | missense_variant | 10/12 | 5 | NM_006279.5 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152114Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251452Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135904
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461890Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727244
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152232Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74452
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 28, 2021 | This sequence change replaces isoleucine with phenylalanine at codon 269 of the ST3GAL3 protein (p.Ile269Phe). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with ST3GAL3-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Benign
DEOGEN2
Benign
T;.;.;.;.;.;.;.;T;.;.;.;.;T;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D;D;D;D;D;D;D;.;D;D;D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.;.;.;.;.;.;N;.;.;.;.;N;.;.;.
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
.;N;N;N;.;.;.;N;.;.;N;.;.;.;N;.;.
REVEL
Benign
Sift
Benign
.;T;T;T;.;.;.;D;.;.;T;.;.;.;T;.;.
Sift4G
Benign
.;T;T;T;.;.;.;.;.;.;T;.;.;.;T;.;.
Polyphen
B;B;D;B;.;.;D;B;B;.;B;.;.;B;.;.;.
Vest4
0.66, 0.65, 0.67, 0.68
MutPred
Loss of ubiquitination at K264 (P = 0.1264);.;.;.;Loss of ubiquitination at K264 (P = 0.1264);.;.;.;Loss of ubiquitination at K264 (P = 0.1264);Loss of ubiquitination at K264 (P = 0.1264);.;.;Loss of ubiquitination at K264 (P = 0.1264);Loss of ubiquitination at K264 (P = 0.1264);.;.;.;
MVP
MPC
1.2
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at