rs839761

Positions:

• chr1-43398186-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365999.1(SZT2):​c.28-4991G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,122 control chromosomes in the GnomAD database, including 10,157 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (10157 hom., cov: 32)
• Consequence: SZT2 NM_001365999.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SZT2	NM_001365999.1	c.28-4991G>A		intron_variant		ENST00000634258.3
SZT2	NM_015284.4	c.28-4991G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SZT2	ENST00000634258.3	c.28-4991G>A		intron_variant		5	NM_001365999.1	P1

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54126 AN: 152004 Hom.: 10153 Cov.: 32

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.0995

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.407

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.356 AC: 54163 AN: 152122 Hom.: 10157 Cov.: 32 AF XY: 0.351 AC XY: 26090 AN XY: 74392

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.426

Gnomad4 EAS AF: 0.0993

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.417

Gnomad4 OTH AF: 0.405

Alfa AF: 0.382 Hom.: 1404

Bravo AF: 0.357

Asia WGS AF: 0.152 AC: 528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.8
DANN	Benign	0.72

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

Other links and lift over

dbSNP: rs839761; hg19: chr1-43863857;