1-43439615-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001365999.1(SZT2):c.6888C>T(p.Cys2296Cys) variant causes a synonymous change. The variant allele was found at a frequency of 0.0233 in 1,613,892 control chromosomes in the GnomAD database, including 507 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 39 hom., cov: 33)

Exomes 𝑓: 0.024 ( 468 hom. )

Consequence

SZT2
NM_001365999.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.48

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 -16 ACMG points.

BP6

Variant 1-43439615-C-T is Benign according to our data. Variant chr1-43439615-C-T is described in ClinVar as Benign. ClinVar VariationId is 241036.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0193 (2939/152330) while in subpopulation NFE AF = 0.0277 (1884/68012). AF 95% confidence interval is 0.0267. There are 39 homozygotes in GnomAd4. There are 1461 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 39 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365999.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SZT2	NM_001365999.1	MANE Select	c.6888C>T	p.Cys2296Cys	synonymous	Exon 50 of 72	NP_001352928.1
	SZT2	NM_015284.4		c.6717C>T	p.Cys2239Cys	synonymous	Exon 49 of 71	NP_056099.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SZT2	ENST00000634258.3	TSL:5 MANE Select	c.6888C>T	p.Cys2296Cys	synonymous	Exon 50 of 72	ENSP00000489255.1
SZT2	ENST00000562955.2	TSL:5	c.6717C>T	p.Cys2239Cys	synonymous	Exon 49 of 71	ENSP00000457168.1
SZT2	ENST00000471177.1	TSL:4	n.551C>T		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes

AF:

0.0193

AC:

2940

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00458

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0205

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00558

Gnomad FIN

AF:

0.0417

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0277

Gnomad OTH

AF:

0.0177

GnomAD2 exomes

AF:

0.0203

AC:

5086

AN:

250364

AF XY:

0.0206

show subpopulations

Gnomad AFR exome

AF:

0.00370

Gnomad AMR exome

AF:

0.0103

Gnomad ASJ exome

AF:

0.0132

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0439

Gnomad NFE exome

AF:

0.0288

Gnomad OTH exome

AF:

0.0239

GnomAD4 exome

AF:

0.0237

AC:

34598

AN:

1461562

Hom.:

468

Cov.:

AF XY:

0.0234

AC XY:

16994

AN XY:

727078

show subpopulations

African (AFR)

AF:

0.00311

AC:

104

AN:

33480

American (AMR)

AF:

0.0110

AC:

492

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.0130

AC:

339

AN:

26100

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.00651

AC:

561

AN:

86226

European-Finnish (FIN)

AF:

0.0428

AC:

2288

AN:

53402

Middle Eastern (MID)

AF:

0.0154

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0266

AC:

29519

AN:

1111822

Other (OTH)

AF:

0.0199

AC:

1204

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

1891

3781

5672

7562

9453

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1054

2108

3162

4216

5270

<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:

0.0193

AC:

2939

AN:

152330

Hom.:

Cov.:

AF XY:

0.0196

AC XY:

1461

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.00457

AC:

190

AN:

41594

American (AMR)

AF:

0.0204

AC:

313

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0101

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.00559

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0417

AC:

443

AN:

10616

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0277

AC:

1884

AN:

68012

Other (OTH)

AF:

0.0175

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

145

290

434

579

724

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<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:

0.0246

Hom.:

Bravo

AF:

0.0171

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.0257

EpiControl

AF:

0.0260

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Jul 24, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Aug 14, 2017

Athena Diagnostics

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

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

May 06, 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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.64

PhyloP100

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=94/6

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.22

Position offset: 11

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over