rs839757

Variant names:

• chr1-43391429-G-A
• rs839757
• NM_001365999.1:c.27+1434G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-43391429-G-A
• chr1-43391429-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365999.1(SZT2):​c.27+1434G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 152,120 control chromosomes in the GnomAD database, including 32,953 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 0.66 (32953 hom., cov: 32)
• Consequence: SZT2 NM_001365999.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.376
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 18

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina, PanelApp Australia
• genetic developmental and epileptic encephalopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365999.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SZT2	NM_001365999.1	MANE Select	c.27+1434G>A		intron	N/A	NP_001352928.1	Q5T011-1
	SZT2	NM_015284.4		c.27+1434G>A		intron	N/A	NP_056099.3	Q5T011-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SZT2	ENST00000634258.3	TSL:5 MANE Select	c.27+1434G>A		intron	N/A	ENSP00000489255.1	Q5T011-1
	SZT2	ENST00000372450.8	TSL:1	c.27+1434G>A		intron	N/A	ENSP00000361528.4	Q5T011-7
	SZT2	ENST00000357658.4	TSL:1	n.45+1434G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99725 AN: 152000 Hom.: 32913 Cov.: 32

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.658

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.673

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

GnomAD4 genome AF: 0.656 AC: 99833 AN: 152120 Hom.: 32953 Cov.: 32 AF XY: 0.653 AC XY: 48571 AN XY: 74350

African (AFR) AF: 0.686 AC: 28435 AN: 41474

American (AMR) AF: 0.642 AC: 9822 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.658 AC: 2285 AN: 3472

East Asian (EAS) AF: 0.523 AC: 2709 AN: 5178

South Asian (SAS) AF: 0.499 AC: 2402 AN: 4816

European-Finnish (FIN) AF: 0.686 AC: 7259 AN: 10586

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.658 AC: 44717 AN: 67982

Other (OTH) AF: 0.674 AC: 1427 AN: 2116

Alfa AF: 0.655 Hom.: 5743

Bravo AF: 0.657

Asia WGS AF: 0.518 AC: 1803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.7
DANN	Benign	0.49
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs839757; hg19: chr1-43857100;