Variant 1-43437918-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001365999.1(SZT2):c.6508+16G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 1,613,306 control chromosomes in the GnomAD database, including 122,461 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8871 hom., cov: 32)

Exomes 𝑓: 0.38 ( 113590 hom. )

Consequence

SZT2
NM_001365999.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.735

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 (HGNC:):

SZT2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 1-43437918-G-T is Benign according to our data. Variant chr1-43437918-G-T is described in ClinVar as [Benign]. Clinvar id is 260620.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SZT2	NM_001365999.1 linkuse as main transcript	c.6508+16G>T		intron_variant		ENST00000634258.3	NP_001352928.1
SZT2	NM_015284.4 linkuse as main transcript	c.6337+16G>T		intron_variant			NP_056099.3	Q5T011-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SZT2	ENST00000634258.3 linkuse as main transcript	c.6508+16G>T		intron_variant		5	NM_001365999.1	ENSP00000489255.1		Q5T011-1

Frequencies

GnomAD3 genomes

AF:

0.323

AC:

48979

AN:

151834

Hom.:

8872

Cov.:

show subpopulations

Gnomad AFR

AF:

0.180

Gnomad AMI

AF:

0.423

Gnomad AMR

AF:

0.387

Gnomad ASJ

AF:

0.425

Gnomad EAS

AF:

0.0735

Gnomad SAS

AF:

0.145

Gnomad FIN

AF:

0.391

Gnomad MID

AF:

0.436

Gnomad NFE

AF:

0.407

Gnomad OTH

AF:

0.378

GnomAD3 exomes

AF:

0.328

AC:

82336

AN:

250836

Hom.:

15488

AF XY:

0.327

AC XY:

44299

AN XY:

135528

show subpopulations

Gnomad AFR exome

AF:

0.172

Gnomad AMR exome

AF:

0.326

Gnomad ASJ exome

AF:

0.436

Gnomad EAS exome

AF:

0.0669

Gnomad SAS exome

AF:

0.154

Gnomad FIN exome

AF:

0.399

Gnomad NFE exome

AF:

0.415

Gnomad OTH exome

AF:

0.372

GnomAD4 exome

AF:

0.384

AC:

560789

AN:

1461354

Hom.:

113590

Cov.:

AF XY:

0.378

AC XY:

274783

AN XY:

726974

show subpopulations

Gnomad4 AFR exome

AF:

0.179

Gnomad4 AMR exome

AF:

0.335

Gnomad4 ASJ exome

AF:

0.433

Gnomad4 EAS exome

AF:

0.100

Gnomad4 SAS exome

AF:

0.158

Gnomad4 FIN exome

AF:

0.392

Gnomad4 NFE exome

AF:

0.419

Gnomad4 OTH exome

AF:

0.363

GnomAD4 genome

AF:

0.322

AC:

49002

AN:

151952

Hom.:

8871

Cov.:

AF XY:

0.318

AC XY:

23652

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.180

Gnomad4 AMR

AF:

0.387

Gnomad4 ASJ

AF:

0.425

Gnomad4 EAS

AF:

0.0734

Gnomad4 SAS

AF:

0.147

Gnomad4 FIN

AF:

0.391

Gnomad4 NFE

AF:

0.407

Gnomad4 OTH

AF:

0.376

Alfa

AF:

0.318

Hom.:

1776

Bravo

AF:

0.320

Asia WGS

AF:

0.131

AC:

457

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Developmental and epileptic encephalopathy, 18

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.21

DANN

Benign

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over