1-43447911-TTGTC-T
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001365999.1(SZT2):c.9508_9511delTGTC(p.Cys3170ThrfsTer70) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
SZT2
NM_001365999.1 frameshift
NM_001365999.1 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.55
Publications
0 publications found
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 was made for transcript
Our verdict: Pathogenic. The variant received 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-43447911-TTGTC-T is Pathogenic according to our data. Variant chr1-43447911-TTGTC-T is described in ClinVar as Pathogenic. ClinVar VariationId is 862427.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001365999.1. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SZT2 | MANE Select | c.9508_9511delTGTC | p.Cys3170ThrfsTer70 | frameshift | Exon 68 of 72 | NP_001352928.1 | Q5T011-1 | ||
| SZT2 | c.9337_9340delTGTC | p.Cys3113ThrfsTer70 | frameshift | Exon 67 of 71 | NP_056099.3 | Q5T011-5 | |||
| SZT2-AS1 | n.560_563delGACA | non_coding_transcript_exon | Exon 2 of 2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SZT2 | TSL:5 MANE Select | c.9508_9511delTGTC | p.Cys3170ThrfsTer70 | frameshift | Exon 68 of 72 | ENSP00000489255.1 | Q5T011-1 | ||
| SZT2 | TSL:5 | c.9337_9340delTGTC | p.Cys3113ThrfsTer70 | frameshift | Exon 67 of 71 | ENSP00000457168.1 | Q5T011-5 | ||
| SZT2-AS1 | TSL:3 | n.560_563delGACA | non_coding_transcript_exon | Exon 2 of 2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461884Hom.: 0 AF XY: 0.00000275 AC XY: 2AN XY: 727242 show subpopulations
GnomAD4 exome
AF:
AC:
3
AN:
1461884
Hom.:
AF XY:
AC XY:
2
AN XY:
727242
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53410
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
3
AN:
1112012
Other (OTH)
AF:
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.492
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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4
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8
10
<30
30-35
35-40
40-45
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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