rs2039531

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

10 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 -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 VariationId 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 rank	MANE	Protein	UniProt
SZT2	NM_001365999.1 link	c.6034+11A>C		intron_variant	Intron 42 of 71	ENST00000634258.3	NP_001352928.1
SZT2	NM_015284.4 link	c.5863+11A>C		intron_variant	Intron 41 of 70		NP_056099.3	Q5T011-5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SZT2	ENST00000634258.3 link	c.6034+11A>C	intron_variant	Intron 42 of 71	5	NM_001365999.1	ENSP00000489255.1	Q5T011-1
SZT2	ENST00000562955.2 link	c.5863+11A>C	intron_variant	Intron 41 of 70	5		ENSP00000457168.1	Q5T011-5
SZT2	ENST00000648058.1 link	n.2488+11A>C	intron_variant	Intron 10 of 39
SZT2	ENST00000649403.1 link	n.784+11A>C	intron_variant	Intron 7 of 36

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

GnomAD2 exomes

AF:

0.325

AC:

81260

AN:

249812

AF XY:

0.325

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 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

African (AFR)

AF:

0.138

AC:

4628

AN:

33466

American (AMR)

AF:

0.334

AC:

14889

AN:

44642

Ashkenazi Jewish (ASJ)

AF:

0.433

AC:

11313

AN:

26126

East Asian (EAS)

AF:

0.100

AC:

3988

AN:

39684

South Asian (SAS)

AF:

0.158

AC:

13590

AN:

86200

European-Finnish (FIN)

AF:

0.392

AC:

20825

AN:

53080

Middle Eastern (MID)

AF:

0.395

AC:

2271

AN:

5756

European-Non Finnish (NFE)

AF:

0.419

AC:

465661

AN:

1111378

Other (OTH)

AF:

0.360

AC:

21733

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

17092

34183

51275

68366

85458

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13976

27952

41928

55904

69880

<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:

0.312

AC:

47415

AN:

152048

Hom.:

8608

Cov.:

AF XY:

0.308

AC XY:

22878

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.142

AC:

5897

AN:

41474

American (AMR)

AF:

0.381

AC:

5823

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.426

AC:

1475

AN:

3466

East Asian (EAS)

AF:

0.0743

AC:

384

AN:

5170

South Asian (SAS)

AF:

0.147

AC:

707

AN:

4818

European-Finnish (FIN)

AF:

0.391

AC:

4135

AN:

10564

Middle Eastern (MID)

AF:

0.442

AC:

130

AN:

294

European-Non Finnish (NFE)

AF:

0.408

AC:

27703

AN:

67962

Other (OTH)

AF:

0.369

AC:

777

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1618

3236

4855

6473

8091

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

464

928

1392

1856

2320

<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:

0.298

Hom.:

1380

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

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

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

9.1

(source)

DANN

Benign

0.63

PhyloP100

0.17

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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