Menu
GeneBe

rs147419780

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_001365999.1(SZT2):c.8916+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000134 in 1,613,566 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 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 0.00069 ( 1 hom., cov: 33)
Exomes 𝑓: 0.000077 ( 0 hom. )

Consequence

SZT2
NM_001365999.1 splice_region, intron

Scores

2
Splicing: ADA: 0.00002741
2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -1.72
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 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=-0.87).
BP6
Variant 1-43445992-G-A is Benign according to our data. Variant chr1-43445992-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 212367.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SZT2NM_001365999.1 linkuse as main transcriptc.8916+8G>A splice_region_variant, intron_variant ENST00000634258.3
SZT2NM_015284.4 linkuse as main transcriptc.8745+8G>A splice_region_variant, intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SZT2ENST00000634258.3 linkuse as main transcriptc.8916+8G>A splice_region_variant, intron_variant 5 NM_001365999.1 P1Q5T011-1

Frequencies

GnomAD3 genomes
AF:
0.000690
AC:
105
AN:
152234
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00239
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000159
AC:
40
AN:
251096
Hom.:
0
AF XY:
0.000103
AC XY:
14
AN XY:
135734
show subpopulations
Gnomad AFR exome
AF:
0.00222
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000766
AC:
112
AN:
1461214
Hom.:
0
Cov.:
30
AF XY:
0.0000592
AC XY:
43
AN XY:
726916
show subpopulations
Gnomad4 AFR exome
AF:
0.00293
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.000149
GnomAD4 genome
AF:
0.000689
AC:
105
AN:
152352
Hom.:
1
Cov.:
33
AF XY:
0.000658
AC XY:
49
AN XY:
74512
show subpopulations
Gnomad4 AFR
AF:
0.00238
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000845
Hom.:
0
Bravo
AF:
0.000808

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoApr 03, 2015- -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeDec 26, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
Cadd
Benign
0.21
Dann
Benign
0.81

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000027
dbscSNV1_RF
Benign
0.0020
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: rs147419780; hg19: chr1-43911663; API