rs114863461

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001365999.1(SZT2):c.2929+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00252 in 1,613,792 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 51 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 37 hom. )

Consequence

SZT2
NM_001365999.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.250

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 1-43425958-G-A is Benign according to our data. Variant chr1-43425958-G-A is described in ClinVar as [Benign]. Clinvar id is 260615.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-43425958-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0135 (2062/152244) while in subpopulation AFR AF= 0.0472 (1958/41524). AF 95% confidence interval is 0.0454. There are 51 homozygotes in gnomad4. There are 945 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 50 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SZT2	NM_001365999.1 linkuse as main transcript	c.2929+9G>A		intron_variant		ENST00000634258.3
SZT2	NM_015284.4 linkuse as main transcript	c.2929+9G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
SZT2	ENST00000634258.3 linkuse as main transcript	c.2929+9G>A	intron_variant	5	NM_001365999.1	P1	Q5T011-1
SZT2	ENST00000562955.2 linkuse as main transcript	c.2929+9G>A	intron_variant	5			Q5T011-5
SZT2	ENST00000470139.1 linkuse as main transcript	c.1660+9G>A	intron_variant, NMD_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0135

AC:

2057

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0471

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00484

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00345

AC:

868

AN:

251380

Hom.:

AF XY:

0.00250

AC XY:

340

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.0479

Gnomad AMR exome

AF:

0.00188

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000616

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00137

AC:

2001

AN:

1461548

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

883

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.0481

Gnomad4 AMR exome

AF:

0.00257

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000459

Gnomad4 OTH exome

AF:

0.00315

GnomAD4 genome

AF:

0.0135

AC:

2062

AN:

152244

Hom.:

Cov.:

AF XY:

0.0127

AC XY:

945

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0472

Gnomad4 AMR

AF:

0.00477

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00694

Hom.:

Bravo

AF:

0.0158

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Mar 05, 2018	- -

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

-0.80

Cadd

Benign

Dann

Benign

0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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