2-85840154-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003896.4(ST3GAL5):c.1247G>A(p.Arg416His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 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. R416L) has been classified as Uncertain significance.
Frequency
Consequence
NM_003896.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ST3GAL5 | NM_003896.4 | c.1247G>A | p.Arg416His | missense_variant | 7/7 | ENST00000638572.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ST3GAL5 | ENST00000638572.2 | c.1247G>A | p.Arg416His | missense_variant | 7/7 | 1 | NM_003896.4 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251388Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135866
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461878Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727238
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
GM3 synthase deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 416 of the ST3GAL5 protein (p.Arg416His). This variant is present in population databases (rs200683924, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with ST3GAL5-related conditions. ClinVar contains an entry for this variant (Variation ID: 649422). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. - |
Seizure Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | New York Genome Center | Jan 23, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at