Variant rs2039531 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001365999.1(SZT2):c.6034+11A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 1,612,742 control chromosomes in the GnomAD database, including 121,820 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 8608 hom., cov: 33)

Exomes 𝑓: 0.38 ( 113212 hom. )

Consequence

SZT2
NM_001365999.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.166

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 1-43435340-A-C is Benign according to our data. Variant chr1-43435340-A-C is described in ClinVar as [Benign]. Clinvar id is 260619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SZT2	NM_001365999.1 link	c.6034+11A>C		intron_variant		ENST00000634258.3	NP_001352928.1
SZT2	NM_015284.4 link	c.5863+11A>C		intron_variant			NP_056099.3	Q5T011-5

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
SZT2	ENST00000634258.3 link	c.6034+11A>C	intron_variant	5	NM_001365999.1	ENSP00000489255.1	Q5T011-1
SZT2	ENST00000562955.2 link	c.5863+11A>C	intron_variant	5		ENSP00000457168.1	Q5T011-5
SZT2	ENST00000648058.1 link	n.2488+11A>C	intron_variant
SZT2	ENST00000649403.1 link	n.784+11A>C	intron_variant

Frequencies

GnomAD3 genomes

AF:

0.312

AC:

47397

AN:

151930

Hom.:

8610

Cov.:

show subpopulations

Gnomad AFR

AF:

0.142

Gnomad AMI

AF:

0.423

Gnomad AMR

AF:

0.381

Gnomad ASJ

AF:

0.426

Gnomad EAS

AF:

0.0743

Gnomad SAS

AF:

0.145

Gnomad FIN

AF:

0.391

Gnomad MID

AF:

0.434

Gnomad NFE

AF:

0.408

Gnomad OTH

AF:

0.371

GnomAD3 exomes

AF:

0.325

AC:

81260

AN:

249812

Hom.:

15248

AF XY:

0.325

AC XY:

43846

AN XY:

135008

show subpopulations

Gnomad AFR exome

AF:

0.134

Gnomad AMR exome

AF:

0.324

Gnomad ASJ exome

AF:

0.436

Gnomad EAS exome

AF:

0.0669

Gnomad SAS exome

AF:

0.154

Gnomad FIN exome

AF:

0.400

Gnomad NFE exome

AF:

0.415

Gnomad OTH exome

AF:

0.370

GnomAD4 exome

AF:

0.383

AC:

558898

AN:

1460694

Hom.:

113212

Cov.:

AF XY:

0.377

AC XY:

273944

AN XY:

726630

show subpopulations

Gnomad4 AFR exome

AF:

0.138

Gnomad4 AMR exome

AF:

0.334

Gnomad4 ASJ exome

AF:

0.433

Gnomad4 EAS exome

AF:

0.100

Gnomad4 SAS exome

AF:

0.158

Gnomad4 FIN exome

AF:

0.392

Gnomad4 NFE exome

AF:

0.419

Gnomad4 OTH exome

AF:

0.360

GnomAD4 genome

AF:

0.312

AC:

47415

AN:

152048

Hom.:

8608

Cov.:

AF XY:

0.308

AC XY:

22878

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.142

Gnomad4 AMR

AF:

0.381

Gnomad4 ASJ

AF:

0.426

Gnomad4 EAS

AF:

0.0743

Gnomad4 SAS

AF:

0.147

Gnomad4 FIN

AF:

0.391

Gnomad4 NFE

AF:

0.408

Gnomad4 OTH

AF:

0.369

Alfa

AF:

0.302

Hom.:

1368

Bravo

AF:

0.307

Asia WGS

AF:

0.129

AC:

448

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Developmental and epileptic encephalopathy, 18

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

9.1

DANN

Benign

0.63

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over