rs780736141
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_001365999.1(SZT2):c.2930-4G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,613,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
SZT2
NM_001365999.1 splice_region, splice_polypyrimidine_tract, intron
NM_001365999.1 splice_region, splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00001081
2
Clinical Significance
Conservation
PhyloP100: -0.511
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 -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 1-43426034-G-A is Benign according to our data. Variant chr1-43426034-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 416977.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| SZT2 | NM_001365999.1 | c.2930-4G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000634258.3 | NP_001352928.1 | |||
| SZT2 | NM_015284.4 | c.2930-4G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | NP_056099.3 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| SZT2 | ENST00000634258.3 | c.2930-4G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_001365999.1 | ENSP00000489255 | P1 | |||
| SZT2 | ENST00000562955.2 | c.2930-4G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | ENSP00000457168 | |||||
| SZT2 | ENST00000470139.1 | c.1661-4G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant | 2 | ENSP00000492726 |
Frequencies
GnomAD3 genomes 0.0000461 AC: 7AN: 152002Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251400Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135880
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GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461598Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4AN XY: 727122
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GnomAD4 genome 0.0000461 AC: 7AN: 152002Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74232
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 12, 2019 | The c.2930-4G>A intronic variant results from a G to A substitution 4 nucleotides upstream from coding exon 21 in the SZT2 gene. This nucleotide position is poorly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this splice acceptor/donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
not provided Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 20, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at