rs115595942

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.9441-12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00347 in 1,613,892 control chromosomes in the GnomAD database, including 146 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 75 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 71 hom. )

Consequence

SZT2
NM_001365999.1 intron

Scores

Splicing: ADA: 0.00001482

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.569

Publications

2 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 links:

SZT2-AS1 (HGNC:41225): (SZT2 antisense RNA 1)

SZT2-AS1 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=-0.85).

BP6

Variant 1-43447837-C-T is Benign according to our data. Variant chr1-43447837-C-T is described in ClinVar as Benign. ClinVar VariationId is 260628.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SZT2	NM_001365999.1 link	c.9441-12C>T	intron_variant	Intron 67 of 71	ENST00000634258.3	NP_001352928.1
SZT2-AS1	NR_046744.1 link	n.638G>A	non_coding_transcript_exon_variant	Exon 2 of 2
SZT2	NM_015284.4 link	c.9270-12C>T	intron_variant	Intron 66 of 70		NP_056099.3	Q5T011-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SZT2	ENST00000634258.3 link	c.9441-12C>T		intron_variant	Intron 67 of 71	5	NM_001365999.1	ENSP00000489255.1		Q5T011-1

Frequencies

GnomAD3 genomes

AF:

0.0177

AC:

2684

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0607

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00740

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.0124

GnomAD2 exomes

AF:

0.00449

AC:

1128

AN:

251148

AF XY:

0.00331

show subpopulations

Gnomad AFR exome

AF:

0.0597

Gnomad AMR exome

AF:

0.00255

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000405

Gnomad OTH exome

AF:

0.00294

GnomAD4 exome

AF:

0.00200

AC:

2921

AN:

1461726

Hom.:

Cov.:

AF XY:

0.00178

AC XY:

1297

AN XY:

727152

show subpopulations

African (AFR)

AF:

0.0631

AC:

2113

AN:

33480

American (AMR)

AF:

0.00327

AC:

146

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.000209

AC:

AN:

86238

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53354

Middle Eastern (MID)

AF:

0.00503

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000327

AC:

364

AN:

1111960

Other (OTH)

AF:

0.00412

AC:

249

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

173

346

519

692

865

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

216

288

360

<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:

0.0177

AC:

2686

AN:

152166

Hom.:

Cov.:

AF XY:

0.0173

AC XY:

1285

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.0606

AC:

2513

AN:

41490

American (AMR)

AF:

0.00739

AC:

113

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000441

AC:

AN:

68000

Other (OTH)

AF:

0.0123

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

131

262

394

525

656

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.0112

Hom.:

Bravo

AF:

0.0204

Asia WGS

AF:

0.00375

AC:

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 17, 2018

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

- -

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

-0.85

CADD

Benign

8.6

(source)

DANN

Benign

0.61

PhyloP100

-0.57

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000015

dbscSNV1_RF

Benign

0.0040

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