rs369157620
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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.1099G>A(p.Val367Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,613,840 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 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000019 ( 0 hom. )
Consequence
ST3GAL3
NM_006279.5 missense
NM_006279.5 missense
Scores
2
3
11
Clinical Significance
Conservation
PhyloP100: 7.63
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=0.37840092).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ST3GAL3 | NM_006279.5 | c.1099G>A | p.Val367Ile | missense_variant | 12/12 | ENST00000347631.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ST3GAL3 | ENST00000347631.8 | c.1099G>A | p.Val367Ile | missense_variant | 12/12 | 5 | NM_006279.5 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152218Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251408Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135872
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GnomAD4 exome AF: 0.0000192 AC: 28AN: 1461622Hom.: 0 Cov.: 33 AF XY: 0.0000165 AC XY: 12AN XY: 727118
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152218Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74354
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 05, 2017 | The p.V367I variant (also known as c.1099G>A), located in coding exon 11 of the ST3GAL3 gene, results from a G to A substitution at nucleotide position 1099. The valine at codon 367 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. - |
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 19, 2022 | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 367 of the ST3GAL3 protein (p.Val367Ile). This variant is present in population databases (rs369157620, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ST3GAL3-related conditions. ClinVar contains an entry for this variant (Variation ID: 571524). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ST3GAL3 protein function. 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
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T;T;T;T;.
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;N;N;N;N;N
PROVEAN
Benign
N;.;.;.;.;N;N;N
REVEL
Benign
Sift
Pathogenic
D;.;.;.;.;D;D;D
Sift4G
Pathogenic
D;.;.;.;.;D;D;D
Polyphen
0.0040
.;.;.;.;.;B;B;.
Vest4
MVP
ClinPred
D
GERP RS
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