rs114863461
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001365999.1(SZT2):c.2929+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00252 in 1,613,792 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.014 ( 51 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 37 hom. )
Consequence
SZT2
NM_001365999.1 intron
NM_001365999.1 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.250
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
Variant 1-43425958-G-A is Benign according to our data. Variant chr1-43425958-G-A is described in ClinVar as [Benign]. Clinvar id is 260615.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-43425958-G-A is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0135 (2062/152244) while in subpopulation AFR AF= 0.0472 (1958/41524). AF 95% confidence interval is 0.0454. There are 51 homozygotes in gnomad4. There are 945 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 51 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SZT2 | NM_001365999.1 | c.2929+9G>A | intron_variant | ENST00000634258.3 | |||
SZT2 | NM_015284.4 | c.2929+9G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SZT2 | ENST00000634258.3 | c.2929+9G>A | intron_variant | 5 | NM_001365999.1 | P1 | |||
SZT2 | ENST00000562955.2 | c.2929+9G>A | intron_variant | 5 | |||||
SZT2 | ENST00000470139.1 | c.1660+9G>A | intron_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0135 AC: 2057AN: 152126Hom.: 50 Cov.: 32
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GnomAD3 exomes AF: 0.00345 AC: 868AN: 251380Hom.: 11 AF XY: 0.00250 AC XY: 340AN XY: 135862
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GnomAD4 exome AF: 0.00137 AC: 2001AN: 1461548Hom.: 37 Cov.: 32 AF XY: 0.00121 AC XY: 883AN XY: 727096
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GnomAD4 genome ? AF: 0.0135 AC: 2062AN: 152244Hom.: 51 Cov.: 32 AF XY: 0.0127 AC XY: 945AN XY: 74442
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 05, 2018 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Developmental and epileptic encephalopathy, 18 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
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DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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