Variant chr1-43420650-A-G 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.1262-99A>G 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 1,169,220 control chromosomes in the GnomAD database, including 87,628 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 9829 hom., cov: 32)

Exomes 𝑓: 0.38 ( 77799 hom. )

Consequence

SZT2
NM_001365999.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.510

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:

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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=-0.93).

BP6

Variant 1-43420650-A-G is Benign according to our data. Variant chr1-43420650-A-G is described in ClinVar as [Benign]. Clinvar id is 1256943.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	UniProt
SZT2	NM_001365999.1 linkuse as main transcript	c.1262-99A>G		intron_variant		ENST00000634258.3
SZT2	NM_015284.4 linkuse as main transcript	c.1262-99A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
SZT2	ENST00000634258.3 linkuse as main transcript	c.1262-99A>G	intron_variant	5	NM_001365999.1	P1	Q5T011-1
SZT2	ENST00000562955.2 linkuse as main transcript	c.1262-99A>G	intron_variant	5			Q5T011-5
SZT2	ENST00000639852.1 linkuse as main transcript	c.928-99A>G	intron_variant, NMD_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.351

AC:

53340

AN:

151886

Hom.:

9826

Cov.:

show subpopulations

Gnomad AFR

AF:

0.275

Gnomad AMI

AF:

0.425

Gnomad AMR

AF:

0.396

Gnomad ASJ

AF:

0.424

Gnomad EAS

AF:

0.0992

Gnomad SAS

AF:

0.156

Gnomad FIN

AF:

0.391

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.407

Gnomad OTH

AF:

0.405

GnomAD4 exome

AF:

0.380

AC:

386267

AN:

1017216

Hom.:

77799

AF XY:

0.373

AC XY:

189984

AN XY:

509718

show subpopulations

Gnomad4 AFR exome

AF:

0.275

Gnomad4 AMR exome

AF:

0.343

Gnomad4 ASJ exome

AF:

0.423

Gnomad4 EAS exome

AF:

0.122

Gnomad4 SAS exome

AF:

0.160

Gnomad4 FIN exome

AF:

0.389

Gnomad4 NFE exome

AF:

0.414

Gnomad4 OTH exome

AF:

0.368

GnomAD4 genome

AF:

0.351

AC:

53379

AN:

152004

Hom.:

9829

Cov.:

AF XY:

0.346

AC XY:

25715

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.276

Gnomad4 AMR

AF:

0.396

Gnomad4 ASJ

AF:

0.424

Gnomad4 EAS

AF:

0.0990

Gnomad4 SAS

AF:

0.157

Gnomad4 FIN

AF:

0.391

Gnomad4 NFE

AF:

0.407

Gnomad4 OTH

AF:

0.403

Alfa

AF:

0.403

Hom.:

12337

Bravo

AF:

0.352

Asia WGS

AF:

0.152

AC:

528

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

8.1

DANN

Benign

0.66

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

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