1-43432382-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001365999.1(SZT2):c.5385T>G(p.Ser1795Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0289 in 1,600,920 control chromosomes in the GnomAD database, including 772 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 101 hom., cov: 32)

Exomes 𝑓: 0.029 ( 671 hom. )

Consequence

SZT2
NM_001365999.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.589

Publications

7 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=-0.83).

BP6

Variant 1-43432382-T-G is Benign according to our data. Variant chr1-43432382-T-G is described in ClinVar as [Benign]. Clinvar id is 260617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.589 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0314 (4784/152272) while in subpopulation SAS AF = 0.0479 (231/4820). AF 95% confidence interval is 0.0429. There are 101 homozygotes in GnomAd4. There are 2358 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 101 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SZT2	NM_001365999.1 link	c.5385T>G	p.Ser1795Ser	synonymous_variant	Exon 37 of 72	ENST00000634258.3	NP_001352928.1
SZT2	NM_015284.4 link	c.5214T>G	p.Ser1738Ser	synonymous_variant	Exon 36 of 71		NP_056099.3	Q5T011-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SZT2	ENST00000634258.3 link	c.5385T>G	p.Ser1795Ser	synonymous_variant	Exon 37 of 72	5	NM_001365999.1	ENSP00000489255.1		Q5T011-1

Frequencies

GnomAD3 genomes

AF:

0.0314

AC:

4782

AN:

152154

Hom.:

100

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0404

Gnomad AMI

AF:

0.0450

Gnomad AMR

AF:

0.0205

Gnomad ASJ

AF:

0.0692

Gnomad EAS

AF:

0.0194

Gnomad SAS

AF:

0.0481

Gnomad FIN

AF:

0.0236

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0272

Gnomad OTH

AF:

0.0306

GnomAD2 exomes

AF:

0.0295

AC:

6997

AN:

237500

AF XY:

0.0303

show subpopulations

Gnomad AFR exome

AF:

0.0393

Gnomad AMR exome

AF:

0.0150

Gnomad ASJ exome

AF:

0.0616

Gnomad EAS exome

AF:

0.0230

Gnomad FIN exome

AF:

0.0259

Gnomad NFE exome

AF:

0.0290

Gnomad OTH exome

AF:

0.0300

GnomAD4 exome

AF:

0.0287

AC:

41504

AN:

1448648

Hom.:

671

Cov.:

AF XY:

0.0291

AC XY:

20935

AN XY:

720130

show subpopulations

African (AFR)

AF:

0.0431

AC:

1418

AN:

32864

American (AMR)

AF:

0.0161

AC:

678

AN:

42048

Ashkenazi Jewish (ASJ)

AF:

0.0620

AC:

1554

AN:

25062

East Asian (EAS)

AF:

0.0154

AC:

610

AN:

39628

South Asian (SAS)

AF:

0.0402

AC:

3379

AN:

84116

European-Finnish (FIN)

AF:

0.0245

AC:

1296

AN:

52984

Middle Eastern (MID)

AF:

0.0479

AC:

272

AN:

5676

European-Non Finnish (NFE)

AF:

0.0276

AC:

30485

AN:

1106502

Other (OTH)

AF:

0.0303

AC:

1812

AN:

59768

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

2358

4716

7074

9432

11790

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0314

AC:

4784

AN:

152272

Hom.:

101

Cov.:

AF XY:

0.0317

AC XY:

2358

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0404

AC:

1679

AN:

41548

American (AMR)

AF:

0.0205

AC:

314

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0692

AC:

240

AN:

3470

East Asian (EAS)

AF:

0.0195

AC:

101

AN:

5182

South Asian (SAS)

AF:

0.0479

AC:

231

AN:

4820

European-Finnish (FIN)

AF:

0.0236

AC:

250

AN:

10614

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0272

AC:

1853

AN:

68020

Other (OTH)

AF:

0.0303

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

225

451

676

902

1127

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0290

Hom.:

158

Bravo

AF:

0.0313

Asia WGS

AF:

0.0240

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 18, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Mar 21, 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

-0.83

CADD

Benign

7.9

(source)

DANN

Benign

0.66

PhyloP100

0.59

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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1-43432382-T-G

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