rs779300816
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006279.5(ST3GAL3):āc.1091A>Gā(p.Lys364Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,613,930 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 (ā ā ).
Frequency
Genomes: š 0.000020 ( 0 hom., cov: 33)
Exomes š: 0.0000027 ( 0 hom. )
Consequence
ST3GAL3
NM_006279.5 missense
NM_006279.5 missense
Scores
2
12
Clinical Significance
Conservation
PhyloP100: 3.76
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 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.2101205).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ST3GAL3 | NM_006279.5 | c.1091A>G | p.Lys364Arg | missense_variant | 12/12 | ENST00000347631.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ST3GAL3 | ENST00000347631.8 | c.1091A>G | p.Lys364Arg | missense_variant | 12/12 | 5 | NM_006279.5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152194Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251456Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135906
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461736Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727174
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152194Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74342
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 20, 2013 | - - |
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 01, 2020 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with ST3GAL3-related disease. ClinVar contains an entry for this variant (Variation ID: 212315). This variant is present in population databases (rs779300816, ExAC 0.003%). This sequence change replaces lysine with arginine at codon 364 of the ST3GAL3 protein (p.Lys364Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.;.;.;.;.;.;T;.;.;T;.;.;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;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;D;D;N;N;N
PrimateAI
Uncertain
T
REVEL
Benign
Polyphen
B;B;B;B;.;B;B;B;B;B;B;.;B;.;B;B;.;.
Vest4
0.28, 0.14, 0.15, 0.17, 0.15, 0.29
MutPred
Gain of catalytic residue at K364 (P = 0.0482);.;.;.;.;.;.;.;.;Gain of catalytic residue at K364 (P = 0.0482);.;.;Gain of catalytic residue at K364 (P = 0.0482);.;.;.;.;.;
MVP
MPC
0.48
ClinPred
D
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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