1-43433158-G-T
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_001365999.1(SZT2):c.5772G>T(p.Leu1924=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000044 in 1,613,994 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000036 ( 0 hom. )
Consequence
SZT2
NM_001365999.1 synonymous
NM_001365999.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.327
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 Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
Variant 1-43433158-G-T is Benign according to our data. Variant chr1-43433158-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 212365.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=4, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=0.327 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SZT2 | NM_001365999.1 | c.5772G>T | p.Leu1924= | synonymous_variant | 40/72 | ENST00000634258.3 | |
SZT2 | NM_015284.4 | c.5601G>T | p.Leu1867= | synonymous_variant | 39/71 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SZT2 | ENST00000634258.3 | c.5772G>T | p.Leu1924= | synonymous_variant | 40/72 | 5 | NM_001365999.1 | P1 | |
SZT2 | ENST00000562955.2 | c.5601G>T | p.Leu1867= | synonymous_variant | 39/71 | 5 | |||
SZT2 | ENST00000648058.1 | n.1031G>T | non_coding_transcript_exon_variant | 9/40 | |||||
SZT2 | ENST00000649403.1 | n.522G>T | non_coding_transcript_exon_variant | 5/37 |
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 152192Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000796 AC: 20AN: 251360Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135868
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GnomAD4 exome AF: 0.0000363 AC: 53AN: 1461684Hom.: 0 Cov.: 32 AF XY: 0.0000426 AC XY: 31AN XY: 727144
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GnomAD4 genome AF: 0.000118 AC: 18AN: 152310Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74470
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2023 | SZT2: BP4, BP7 - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 03, 2015 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 06, 2018 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
SZT2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 14, 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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Benign
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RBP_binding_hub_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at