rs760427137
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong
The NM_001365999.1(SZT2):c.5516G>A(p.Arg1839His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000775 in 1,613,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 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. R1839C) has been classified as Uncertain significance.
Frequency
Consequence
NM_001365999.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SZT2 | NM_001365999.1 | c.5516G>A | p.Arg1839His | missense_variant | 38/72 | ENST00000634258.3 | |
SZT2 | NM_015284.4 | c.5345G>A | p.Arg1782His | missense_variant | 37/71 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SZT2 | ENST00000634258.3 | c.5516G>A | p.Arg1839His | missense_variant | 38/72 | 5 | NM_001365999.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000789 AC: 12AN: 152156Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000519 AC: 13AN: 250428Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135388
GnomAD4 exome AF: 0.0000773 AC: 113AN: 1461404Hom.: 0 Cov.: 33 AF XY: 0.0000701 AC XY: 51AN XY: 727032
GnomAD4 genome ? AF: 0.0000789 AC: 12AN: 152156Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74336
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 18 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 28, 2017 | The p.R1782H variant (also known as c.5345G>A), located in coding exon 37 of the SZT2 gene, results from a G to A substitution at nucleotide position 5345. The arginine at codon 1782 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is well 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 alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 20, 2022 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1782 of the SZT2 protein (p.Arg1782His). This variant is present in population databases (rs760427137, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SZT2-related conditions. ClinVar contains an entry for this variant (Variation ID: 521493). 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:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at