1-43390239-C-T

Variant names:

• chr1-43390239-C-T
• rs839754
• NM_001365999.1:c.27+244C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001365999.1(SZT2):​c.27+244C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 152,164 control chromosomes in the GnomAD database, including 8,508 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.33 (8508 hom., cov: 33)
• Consequence: SZT2 NM_001365999.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0230
• Publications: 12 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-43390239-C-T is Benign according to our data. Variant chr1-43390239-C-T is described in ClinVar as [Benign]. Clinvar id is 1295756.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SZT2	NM_001365999.1	c.27+244C>T		intron_variant	Intron 1 of 71	ENST00000634258.3	NP_001352928.1
SZT2	NM_015284.4	c.27+244C>T		intron_variant	Intron 1 of 70		NP_056099.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SZT2	ENST00000634258.3	c.27+244C>T		intron_variant	Intron 1 of 71	5	NM_001365999.1	ENSP00000489255.1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49815 AN: 152046 Hom.: 8503 Cov.: 33

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.100

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.328 AC: 49852 AN: 152164 Hom.: 8508 Cov.: 33 AF XY: 0.323 AC XY: 24011 AN XY: 74390

African (AFR) AF: 0.271 AC: 11246 AN: 41522

American (AMR) AF: 0.372 AC: 5693 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1409 AN: 3468

East Asian (EAS) AF: 0.100 AC: 519 AN: 5192

South Asian (SAS) AF: 0.149 AC: 719 AN: 4828

European-Finnish (FIN) AF: 0.332 AC: 3512 AN: 10568

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.375 AC: 25479 AN: 67982

Other (OTH) AF: 0.379 AC: 799 AN: 2110

Alfa AF: 0.345 Hom.: 1202

Bravo AF: 0.331

Asia WGS AF: 0.146 AC: 509 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 15, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.9
DANN	Benign	0.88
PhyloP100		0.023
PromoterAI		0.032	Neutral
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: rs839754; hg19: chr1-43855910;