2-85840154-C-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_003896.4(ST3GAL5):c.1247G>T(p.Arg416Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000594 in 1,614,058 control chromosomes in the GnomAD database, including 1 homozygotes. 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. R416C) has been classified as Uncertain significance.
Frequency
Consequence
NM_003896.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ST3GAL5 | NM_003896.4 | c.1247G>T | p.Arg416Leu | missense_variant | 7/7 | ENST00000638572.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ST3GAL5 | ENST00000638572.2 | c.1247G>T | p.Arg416Leu | missense_variant | 7/7 | 1 | NM_003896.4 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000243 AC: 37AN: 152180Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000402 AC: 101AN: 251388Hom.: 0 AF XY: 0.000383 AC XY: 52AN XY: 135866
GnomAD4 exome AF: 0.000630 AC: 921AN: 1461878Hom.: 1 Cov.: 31 AF XY: 0.000582 AC XY: 423AN XY: 727238
GnomAD4 genome AF: 0.000243 AC: 37AN: 152180Hom.: 0 Cov.: 32 AF XY: 0.000256 AC XY: 19AN XY: 74352
ClinVar
Submissions by phenotype
GM3 synthase deficiency Uncertain:4
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 04, 2019 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 20, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 24, 2022 | This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 416 of the ST3GAL5 protein (p.Arg416Leu). This variant is present in population databases (rs200683924, gnomAD 0.08%). 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: 198500). 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 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. - |
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 03, 2015 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 14, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 29, 2019 | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 06, 2014 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 14, 2022 | The c.1247G>T (p.R416L) alteration is located in exon 7 (coding exon 7) of the ST3GAL5 gene. This alteration results from a G to T substitution at nucleotide position 1247, causing the arginine (R) at amino acid position 416 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at