rs533632273

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_001365999.1(SZT2):ā€‹c.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

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0910
Variant links:
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]

Genome browser will be placed here

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
SZT2NM_001365999.1 linkuse as main transcriptc.1107A>G p.Leu369Leu synonymous_variant 9/72 ENST00000634258.3 NP_001352928.1
SZT2NM_015284.4 linkuse as main transcriptc.1107A>G p.Leu369Leu synonymous_variant 9/71 NP_056099.3 Q5T011-5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SZT2ENST00000634258.3 linkuse as main transcriptc.1107A>G p.Leu369Leu synonymous_variant 9/725 NM_001365999.1 ENSP00000489255.1 Q5T011-1
SZT2ENST00000562955.2 linkuse as main transcriptc.1107A>G p.Leu369Leu synonymous_variant 9/715 ENSP00000457168.1 Q5T011-5
SZT2ENST00000639852.1 linkuse as main transcriptn.773A>G non_coding_transcript_exon_variant 6/95 ENSP00000492385.1 A0A1W2PQY2

Frequencies

GnomAD3 genomes
AF:
0.000138
AC:
21
AN:
152174
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00373
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000314
AC:
72
AN:
229102
Hom.:
0
AF XY:
0.000427
AC XY:
54
AN XY:
126594
show subpopulations
Gnomad AFR exome
AF:
0.0000716
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00228
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000947
Gnomad OTH exome
AF:
0.000171
GnomAD4 exome
AF:
0.000163
AC:
235
AN:
1446116
Hom.:
0
Cov.:
32
AF XY:
0.000233
AC XY:
168
AN XY:
719780
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00250
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.000182
GnomAD4 genome
AF:
0.000138
AC:
21
AN:
152292
Hom.:
0
Cov.:
33
AF XY:
0.000188
AC XY:
14
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.0000722
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00374
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000378
Asia WGS
AF:
0.00144
AC:
5
AN:
3478

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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 10, 2024- -
Likely benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2021- -
Developmental and epileptic encephalopathy, 18 Benign:1
Likely benign, criteria provided, single submitterclinical testingGenome-Nilou LabApr 11, 2023- -
SZT2-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesFeb 24, 2019This 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

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.62
CADD
Benign
2.4
DANN
Benign
0.38

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs533632273; hg19: chr1-43885840; API