rs2255632

Positions:

chr1-43443594-T-C

Variant summary

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

The NM_001365999.1(SZT2):c.8626-3T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 1,613,750 control chromosomes in the GnomAD database, including 126,714 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 9089 hom., cov: 32)

Exomes 𝑓: 0.39 ( 117625 hom. )

Consequence

SZT2
NM_001365999.1 splice_region, intron

Scores

Splicing: ADA: 0.00003135

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.92

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:

SZT2 (HGNC:):

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=-0.74).

BP6

Variant 1-43443594-T-C is Benign according to our data. Variant chr1-43443594-T-C is described in ClinVar as [Benign]. Clinvar id is 260626.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SZT2	NM_001365999.1 linkuse as main transcript	c.8626-3T>C		splice_region_variant, intron_variant		ENST00000634258.3	NP_001352928.1
SZT2	NM_015284.4 linkuse as main transcript	c.8455-3T>C		splice_region_variant, intron_variant			NP_056099.3	Q5T011-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SZT2	ENST00000634258.3 linkuse as main transcript	c.8626-3T>C		splice_region_variant, intron_variant		5	NM_001365999.1	ENSP00000489255.1		Q5T011-1

Frequencies

GnomAD3 genomes

AF:

0.322

AC:

48915

AN:

151952

Hom.:

9090

Cov.:

show subpopulations

Gnomad AFR

AF:

0.147

Gnomad AMI

AF:

0.480

Gnomad AMR

AF:

0.392

Gnomad ASJ

AF:

0.465

Gnomad EAS

AF:

0.124

Gnomad SAS

AF:

0.158

Gnomad FIN

AF:

0.407

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.414

Gnomad OTH

AF:

0.382

GnomAD3 exomes

AF:

0.337

AC:

84632

AN:

251052

Hom.:

16258

AF XY:

0.337

AC XY:

45706

AN XY:

135726

show subpopulations

Gnomad AFR exome

AF:

0.139

Gnomad AMR exome

AF:

0.330

Gnomad ASJ exome

AF:

0.471

Gnomad EAS exome

AF:

0.112

Gnomad SAS exome

AF:

0.165

Gnomad FIN exome

AF:

0.411

Gnomad NFE exome

AF:

0.422

Gnomad OTH exome

AF:

0.381

GnomAD4 exome

AF:

0.391

AC:

571782

AN:

1461680

Hom.:

117625

Cov.:

AF XY:

0.386

AC XY:

280696

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.135

Gnomad4 AMR exome

AF:

0.340

Gnomad4 ASJ exome

AF:

0.468

Gnomad4 EAS exome

AF:

0.158

Gnomad4 SAS exome

AF:

0.169

Gnomad4 FIN exome

AF:

0.404

Gnomad4 NFE exome

AF:

0.425

Gnomad4 OTH exome

AF:

0.371

GnomAD4 genome

AF:

0.322

AC:

48927

AN:

152070

Hom.:

9089

Cov.:

AF XY:

0.319

AC XY:

23706

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.147

Gnomad4 AMR

AF:

0.392

Gnomad4 ASJ

AF:

0.465

Gnomad4 EAS

AF:

0.123

Gnomad4 SAS

AF:

0.159

Gnomad4 FIN

AF:

0.407

Gnomad4 NFE

AF:

0.414

Gnomad4 OTH

AF:

0.380

Alfa

AF:

0.383

Hom.:

8893

Bravo

AF:

0.317

Asia WGS

AF:

0.148

AC:

517

AN:

3478

EpiCase

AF:

0.426

EpiControl

AF:

0.430

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -
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	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 18, 2018	- -

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

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 08, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000031

dbscSNV1_RF

Benign

0.0060

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