1-43440440-C-T

Variant names:

• chr1-43440440-C-T
• rs116454519
• NM_001365999.1:c.7211-13C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001365999.1(SZT2):​c.7211-13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000281 in 1,421,640 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: SZT2 NM_001365999.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.424
• Publications: 2 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Illumina
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).

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.7211-13C>T		intron	N/A	NP_001352928.1	Q5T011-1
	SZT2	NM_015284.4		c.7040-13C>T		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.7211-13C>T		intron	N/A	ENSP00000489255.1	Q5T011-1
	SZT2	ENST00000562955.2	TSL:5	c.7040-13C>T		intron	N/A	ENSP00000457168.1	Q5T011-5
	SZT2	ENST00000648058.1		n.3665-13C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000458 AC: 1 AN: 218422 AF XY: 0.00000846

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000489

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000281 AC: 4 AN: 1421640 Hom.: 0 Cov.: 31 AF XY: 0.00000284 AC XY: 2 AN XY: 704656

African (AFR) AF: 0.00 AC: 0 AN: 31730

American (AMR) AF: 0.00 AC: 0 AN: 37268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23640

East Asian (EAS) AF: 0.00 AC: 0 AN: 38474

South Asian (SAS) AF: 0.00 AC: 0 AN: 80168

European-Finnish (FIN) AF: 0.0000570 AC: 3 AN: 52606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5594

European-Non Finnish (NFE) AF: 9.14e-7 AC: 1 AN: 1093574

Other (OTH) AF: 0.00 AC: 0 AN: 58586

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	15
DANN	Benign	0.63
PhyloP100		0.42

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: rs116454519; hg19: chr1-43906111;