1-43390239-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001365999.1(SZT2):​c.27+244C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 152,164 control chromosomes in the GnomAD database, including 8,508 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.33 ( 8508 hom., cov: 33)

Consequence

SZT2
NM_001365999.1 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0230

Publications

12 publications found
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]
SZT2 Gene-Disease associations (from GenCC):
  • developmental and epileptic encephalopathy, 18
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Illumina
  • genetic developmental and epileptic encephalopathy
    Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
  • undetermined early-onset epileptic encephalopathy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
Variant 1-43390239-C-T is Benign according to our data. Variant chr1-43390239-C-T is described in ClinVar as [Benign]. Clinvar id is 1295756.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SZT2NM_001365999.1 linkc.27+244C>T intron_variant Intron 1 of 71 ENST00000634258.3 NP_001352928.1
SZT2NM_015284.4 linkc.27+244C>T intron_variant Intron 1 of 70 NP_056099.3 Q5T011-5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SZT2ENST00000634258.3 linkc.27+244C>T intron_variant Intron 1 of 71 5 NM_001365999.1 ENSP00000489255.1 Q5T011-1

Frequencies

GnomAD3 genomes
AF:
0.328
AC:
49815
AN:
152046
Hom.:
8503
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.271
Gnomad AMI
AF:
0.388
Gnomad AMR
AF:
0.373
Gnomad ASJ
AF:
0.406
Gnomad EAS
AF:
0.100
Gnomad SAS
AF:
0.148
Gnomad FIN
AF:
0.332
Gnomad MID
AF:
0.411
Gnomad NFE
AF:
0.375
Gnomad OTH
AF:
0.381
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.328
AC:
49852
AN:
152164
Hom.:
8508
Cov.:
33
AF XY:
0.323
AC XY:
24011
AN XY:
74390
show subpopulations
African (AFR)
AF:
0.271
AC:
11246
AN:
41522
American (AMR)
AF:
0.372
AC:
5693
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
0.406
AC:
1409
AN:
3468
East Asian (EAS)
AF:
0.100
AC:
519
AN:
5192
South Asian (SAS)
AF:
0.149
AC:
719
AN:
4828
European-Finnish (FIN)
AF:
0.332
AC:
3512
AN:
10568
Middle Eastern (MID)
AF:
0.418
AC:
123
AN:
294
European-Non Finnish (NFE)
AF:
0.375
AC:
25479
AN:
67982
Other (OTH)
AF:
0.379
AC:
799
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1770
3541
5311
7082
8852
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
488
976
1464
1952
2440
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.345
Hom.:
1202
Bravo
AF:
0.331
Asia WGS
AF:
0.146
AC:
509
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jul 15, 2018
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
5.9
DANN
Benign
0.88
PhyloP100
0.023
PromoterAI
0.032
Neutral
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs839754; hg19: chr1-43855910; API