rs140366288

Positions:

• chr1-43426818-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001365999.1(SZT2):​c.3309+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 1,612,260 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (6 hom.)
• Consequence: SZT2 NM_001365999.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:3
• Conservation: PhyloP100: -1.34

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-43426818-C-T is Benign according to our data. Variant chr1-43426818-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 416959.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-43426818-C-T is described in Lovd as [Likely_benign].
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SZT2	NM_001365999.1	c.3309+9C>T		intron_variant		ENST00000634258.3
SZT2	NM_015284.4	c.3138+9C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SZT2	ENST00000634258.3	c.3309+9C>T		intron_variant		5	NM_001365999.1	P1
SZT2	ENST00000562955.2	c.3138+9C>T		intron_variant		5
SZT2	ENST00000470139.1	c.*176+9C>T		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00107 AC: 163 AN: 152174 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00210

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000869 AC: 214 AN: 246276 Hom.: 0 AF XY: 0.000863 AC XY: 115 AN XY: 133242

Gnomad AFR exome AF: 0.000377

Gnomad AMR exome AF: 0.000293

Gnomad ASJ exome AF: 0.000101

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000661

Gnomad FIN exome AF: 0.000484

Gnomad NFE exome AF: 0.00147

Gnomad OTH exome AF: 0.000501

GnomAD4 exome AF: 0.00143 AC: 2094 AN: 1459968 Hom.: 6 Cov.: 31 AF XY: 0.00140 AC XY: 1020 AN XY: 726216

Gnomad4 AFR exome AF: 0.000269

Gnomad4 AMR exome AF: 0.000337

Gnomad4 ASJ exome AF: 0.0000768

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000686

Gnomad4 FIN exome AF: 0.000394

Gnomad4 NFE exome AF: 0.00172

Gnomad4 OTH exome AF: 0.00126

GnomAD4 genome AF: 0.00108 AC: 164 AN: 152292 Hom.: 0 Cov.: 32 AF XY: 0.000859 AC XY: 64 AN XY: 74472

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00210

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00148 Hom.: 0

Bravo AF: 0.00106

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:3

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 06, 2024	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.66

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

Other links and lift over

dbSNP: rs140366288; hg19: chr1-43892489;