rs145882968

Positions:

chr1-43442844-C-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001365999.1(SZT2):c.8177C>G(p.Thr2726Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000321 in 1,609,430 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00060 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00029 ( 2 hom. )

Consequence

SZT2
NM_001365999.1 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:4

Conservation

PhyloP100: 4.89

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0062170327).

BP6

Variant 1-43442844-C-G is Benign according to our data. Variant chr1-43442844-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 411936.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-43442844-C-G is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SZT2	NM_001365999.1 link	c.8177C>G	p.Thr2726Ser	missense_variant	59/72	ENST00000634258.3	NP_001352928.1
SZT2	NM_015284.4 link	c.8006C>G	p.Thr2669Ser	missense_variant	58/71		NP_056099.3	Q5T011-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SZT2	ENST00000634258.3 link	c.8177C>G	p.Thr2726Ser	missense_variant	59/72	5	NM_001365999.1	ENSP00000489255.1	Q5T011-1
SZT2	ENST00000562955.2 link	c.8006C>G	p.Thr2669Ser	missense_variant	58/71	5		ENSP00000457168.1	Q5T011-5
SZT2	ENST00000648058.1 link	n.4631C>G		non_coding_transcript_exon_variant	27/40
SZT2	ENST00000649403.1 link	n.2927C>G		non_coding_transcript_exon_variant	24/37

Frequencies

GnomAD3 genomes

AF:

0.000572

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000981

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000428

AC:

106

AN:

247450

Hom.:

AF XY:

0.000329

AC XY:

AN XY:

133644

show subpopulations

Gnomad AFR exome

AF:

0.00154

Gnomad AMR exome

AF:

0.00120

Gnomad ASJ exome

AF:

0.000825

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000334

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000242

Gnomad OTH exome

AF:

0.000663

GnomAD4 exome

AF:

0.000291

AC:

424

AN:

1457150

Hom.:

Cov.:

AF XY:

0.000283

AC XY:

205

AN XY:

724490

show subpopulations

Gnomad4 AFR exome

AF:

0.00156

Gnomad4 AMR exome

AF:

0.00133

Gnomad4 ASJ exome

AF:

0.000582

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000701

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000220

Gnomad4 OTH exome

AF:

0.000665

GnomAD4 genome

AF:

0.000604

AC:

AN:

152280

Hom.:

Cov.:

AF XY:

0.000578

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00120

Gnomad4 AMR

AF:

0.000980

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000455

Hom.:

Bravo

AF:

0.000654

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000379

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 23, 2021	- -

Intellectual disability

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille

Jan 01, 2019

- -

Developmental and epileptic encephalopathy, 18

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2017

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.065

T;.

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.0029

MetaRNN

Benign

0.0062

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.63

N;.

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.58

.;N

Sift

Benign

0.65

.;T

Sift4G

Benign

0.40

T;T

Polyphen

0.0010

.;B

Vest4

0.23

MutPred

0.16

.;Loss of glycosylation at T2669 (P = 0.0171);

MVP

0.28

MPC

0.24

ClinPred

0.013

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.11

gMVP

0.13

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