rs533632273
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_001365999.1(SZT2):āc.1107A>Gā(p.Leu369Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00016 in 1,598,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00014 ( 0 hom., cov: 33)
Exomes š: 0.00016 ( 0 hom. )
Consequence
SZT2
NM_001365999.1 synonymous
NM_001365999.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0910
Genes affected
SZT2 (HGNC:29040): (SZT2 subunit of KICSTOR complex) The protein encoded by this gene is expressed in the brain, predominantly in the parietal and frontal cortex as well as in dorsal root ganglia. It is localized to the peroxisome, and is implicated in resistance to oxidative stress. It likely functions by increasing superoxide dismutase (SOD) activity, but itself has no direct SOD activity. Studies in mice show that this gene confers low seizure threshold, and may also enhance epileptogenesis. [provided by RefSeq, Jun 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
Variant 1-43420169-A-G is Benign according to our data. Variant chr1-43420169-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 416976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.091 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SZT2 | NM_001365999.1 | c.1107A>G | p.Leu369Leu | synonymous_variant | 9/72 | ENST00000634258.3 | NP_001352928.1 | |
SZT2 | NM_015284.4 | c.1107A>G | p.Leu369Leu | synonymous_variant | 9/71 | NP_056099.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SZT2 | ENST00000634258.3 | c.1107A>G | p.Leu369Leu | synonymous_variant | 9/72 | 5 | NM_001365999.1 | ENSP00000489255.1 | ||
SZT2 | ENST00000562955.2 | c.1107A>G | p.Leu369Leu | synonymous_variant | 9/71 | 5 | ENSP00000457168.1 | |||
SZT2 | ENST00000639852.1 | n.773A>G | non_coding_transcript_exon_variant | 6/9 | 5 | ENSP00000492385.1 |
Frequencies
GnomAD3 genomes AF: 0.000138 AC: 21AN: 152174Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000314 AC: 72AN: 229102Hom.: 0 AF XY: 0.000427 AC XY: 54AN XY: 126594
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GnomAD4 exome AF: 0.000163 AC: 235AN: 1446116Hom.: 0 Cov.: 32 AF XY: 0.000233 AC XY: 168AN XY: 719780
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GnomAD4 genome AF: 0.000138 AC: 21AN: 152292Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14AN XY: 74458
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ClinVar
Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 10, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2021 | - - |
Developmental and epileptic encephalopathy, 18 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
SZT2-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 24, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at