rs752495437
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3_Moderate
The NM_001365999.1(SZT2):c.2477G>A(p.Arg826Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. R826R) has been classified as Likely benign.
Frequency
Consequence
NM_001365999.1 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SZT2 | NM_001365999.1 | c.2477G>A | p.Arg826Gln | missense_variant | 17/72 | ENST00000634258.3 | |
SZT2 | NM_015284.4 | c.2477G>A | p.Arg826Gln | missense_variant | 17/71 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SZT2 | ENST00000634258.3 | c.2477G>A | p.Arg826Gln | missense_variant | 17/72 | 5 | NM_001365999.1 | P1 | |
SZT2 | ENST00000562955.2 | c.2477G>A | p.Arg826Gln | missense_variant | 17/71 | 5 | |||
SZT2 | ENST00000470139.1 | c.1208G>A | p.Arg403Gln | missense_variant, NMD_transcript_variant | 8/18 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152100Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251426Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135886
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461698Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727154
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152100Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74290
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 13, 2016 | - - |
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 | Aug 02, 2022 | The c.2477G>A (p.R826Q) alteration is located in exon 17 (coding exon 17) of the SZT2 gene. This alteration results from a G to A substitution at nucleotide position 2477, causing the arginine (R) at amino acid position 826 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 06, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 826 of the SZT2 protein (p.Arg826Gln). This variant is present in population databases (rs752495437, gnomAD 0.003%). 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: 436930). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; 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