rs2027130

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001365999.1(SZT2):c.7356A>G(p.Glu2452Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 1,613,758 control chromosomes in the GnomAD database, including 121,674 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 8558 hom., cov: 32)

Exomes 𝑓: 0.38 ( 113116 hom. )

Consequence

SZT2
NM_001365999.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.742

Publications

20 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

SZT2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 1-43441225-A-G is Benign according to our data. Variant chr1-43441225-A-G is described in ClinVar as Benign. ClinVar VariationId is 260623.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.742 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SZT2	NM_001365999.1 link	c.7356A>G	p.Glu2452Glu	synonymous_variant	Exon 53 of 72	ENST00000634258.3	NP_001352928.1
SZT2	NM_015284.4 link	c.7185A>G	p.Glu2395Glu	synonymous_variant	Exon 52 of 71		NP_056099.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
SZT2	ENST00000634258.3 link	c.7356A>G	p.Glu2452Glu	synonymous_variant	Exon 53 of 72	5	NM_001365999.1	ENSP00000489255.1
SZT2	ENST00000562955.2 link	c.7185A>G	p.Glu2395Glu	synonymous_variant	Exon 52 of 71	5		ENSP00000457168.1
SZT2	ENST00000648058.1 link	n.3810A>G		non_coding_transcript_exon_variant	Exon 21 of 40
SZT2	ENST00000649403.1 link	n.2106A>G		non_coding_transcript_exon_variant	Exon 18 of 37

Frequencies

GnomAD3 genomes

AF:

0.307

AC:

46734

AN:

152050

Hom.:

8558

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.424

Gnomad AMR

AF:

0.383

Gnomad ASJ

AF:

0.425

Gnomad EAS

AF:

0.0742

Gnomad SAS

AF:

0.146

Gnomad FIN

AF:

0.392

Gnomad MID

AF:

0.434

Gnomad NFE

AF:

0.407

Gnomad OTH

AF:

0.366

GnomAD2 exomes

AF:

0.324

AC:

81444

AN:

251228

AF XY:

0.324

show subpopulations

Gnomad AFR exome

AF:

0.117

Gnomad AMR exome

AF:

0.324

Gnomad ASJ exome

AF:

0.437

Gnomad EAS exome

AF:

0.0669

Gnomad FIN exome

AF:

0.399

Gnomad NFE exome

AF:

0.415

Gnomad OTH exome

AF:

0.369

GnomAD4 exome

AF:

0.382

AC:

558195

AN:

1461590

Hom.:

113116

Cov.:

AF XY:

0.376

AC XY:

273731

AN XY:

727074

show subpopulations

African (AFR)

AF:

0.116

AC:

3879

AN:

33470

American (AMR)

AF:

0.333

AC:

14881

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.433

AC:

11317

AN:

26122

East Asian (EAS)

AF:

0.100

AC:

3985

AN:

39696

South Asian (SAS)

AF:

0.158

AC:

13586

AN:

86246

European-Finnish (FIN)

AF:

0.392

AC:

20955

AN:

53412

Middle Eastern (MID)

AF:

0.398

AC:

2292

AN:

5754

European-Non Finnish (NFE)

AF:

0.419

AC:

465640

AN:

1111802

Other (OTH)

AF:

0.359

AC:

21660

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

18897

37794

56692

75589

94486

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13962

27924

41886

55848

69810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.307

AC:

46750

AN:

152168

Hom.:

8558

Cov.:

AF XY:

0.304

AC XY:

22609

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.125

AC:

5200

AN:

41530

American (AMR)

AF:

0.383

AC:

5860

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.425

AC:

1473

AN:

3468

East Asian (EAS)

AF:

0.0742

AC:

384

AN:

5176

South Asian (SAS)

AF:

0.147

AC:

710

AN:

4822

European-Finnish (FIN)

AF:

0.392

AC:

4149

AN:

10580

Middle Eastern (MID)

AF:

0.442

AC:

130

AN:

294

European-Non Finnish (NFE)

AF:

0.407

AC:

27687

AN:

67968

Other (OTH)

AF:

0.364

AC:

770

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1565

3129

4694

6258

7823

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

456

912

1368

1824

2280

<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:

0.364

Hom.:

9504

Bravo

AF:

0.302

Asia WGS

AF:

0.128

AC:

444

AN:

3478

EpiCase

AF:

0.418

EpiControl

AF:

0.422

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 20, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 15, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Developmental and epileptic encephalopathy, 18

Benign:1

Apr 11, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Jan 08, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

DANN

Benign

0.60

PhyloP100

0.74

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over