1-43428384-A-G
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong
The NM_001365999.1(SZT2):āc.4064A>Gā(p.His1355Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,614,144 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 (ā ā ).
Frequency
Consequence
NM_001365999.1 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SZT2 | NM_001365999.1 | c.4064A>G | p.His1355Arg | missense_variant | 28/72 | ENST00000634258.3 | NP_001352928.1 | |
SZT2 | NM_015284.4 | c.3893A>G | p.His1298Arg | missense_variant | 27/71 | NP_056099.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SZT2 | ENST00000634258.3 | c.4064A>G | p.His1355Arg | missense_variant | 28/72 | 5 | NM_001365999.1 | ENSP00000489255.1 | ||
SZT2 | ENST00000562955.2 | c.3893A>G | p.His1298Arg | missense_variant | 27/71 | 5 | ENSP00000457168.1 | |||
SZT2 | ENST00000470139.1 | n.*1199A>G | non_coding_transcript_exon_variant | 18/18 | 2 | ENSP00000492726.1 | ||||
SZT2 | ENST00000470139.1 | n.*1199A>G | 3_prime_UTR_variant | 18/18 | 2 | ENSP00000492726.1 |
Frequencies
GnomAD3 genomes AF: 0.000197 AC: 30AN: 152132Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000676 AC: 17AN: 251494Hom.: 0 AF XY: 0.0000441 AC XY: 6AN XY: 135922
GnomAD4 exome AF: 0.0000150 AC: 22AN: 1461894Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 727248
GnomAD4 genome AF: 0.000197 AC: 30AN: 152250Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74436
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 18 Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Dec 31, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 13, 2022 | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 1298 of the SZT2 protein (p.His1298Arg). This variant is present in population databases (rs149741610, gnomAD 0.08%). 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: 411937). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SZT2 protein function. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Nov 25, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 23, 2024 | In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 25, 2024 | The c.3893A>G (p.H1298R) alteration is located in exon 27 (coding exon 27) of the SZT2 gene. This alteration results from a A to G substitution at nucleotide position 3893, causing the histidine (H) at amino acid position 1298 to be replaced by an arginine (R). 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