Variant chr1-43447837-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001365999.1(SZT2):c.9441-12C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00347 in 1,613,892 control chromosomes in the GnomAD database, including 146 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 75 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 71 hom. )

Consequence

SZT2
NM_001365999.1 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001482

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.569

Variant links:

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 links:

SZT2-AS1 (HGNC:41225): (SZT2 antisense RNA 1)

SZT2-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 1-43447837-C-T is Benign according to our data. Variant chr1-43447837-C-T is described in ClinVar as [Benign]. Clinvar id is 260628.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-43447837-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
SZT2	NM_001365999.1 linkuse as main transcript	c.9441-12C>T	splice_polypyrimidine_tract_variant, intron_variant		ENST00000634258.3	NP_001352928.1
SZT2-AS1	NR_046744.1 linkuse as main transcript	n.638G>A	non_coding_transcript_exon_variant	2/2
SZT2	NM_015284.4 linkuse as main transcript	c.9270-12C>T	splice_polypyrimidine_tract_variant, intron_variant			NP_056099.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SZT2	ENST00000634258.3 linkuse as main transcript	c.9441-12C>T		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001365999.1	ENSP00000489255	P1	Q5T011-1
SZT2-AS1	ENST00000396885.2 linkuse as main transcript	n.638G>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.0177

AC:

2684

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0607

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00740

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.00449

AC:

1128

AN:

251148

Hom.:

AF XY:

0.00331

AC XY:

449

AN XY:

135730

show subpopulations

Gnomad AFR exome

AF:

0.0597

Gnomad AMR exome

AF:

0.00255

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000405

Gnomad OTH exome

AF:

0.00294

GnomAD4 exome

AF:

0.00200

AC:

2921

AN:

1461726

Hom.:

Cov.:

AF XY:

0.00178

AC XY:

1297

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.0631

Gnomad4 AMR exome

AF:

0.00327

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000327

Gnomad4 OTH exome

AF:

0.00412

GnomAD4 genome

AF:

0.0177

AC:

2686

AN:

152166

Hom.:

Cov.:

AF XY:

0.0173

AC XY:

1285

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0606

Gnomad4 AMR

AF:

0.00739

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.00979

Hom.:

Bravo

AF:

0.0204

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 17, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Developmental and epileptic encephalopathy, 18

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

8.6

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000015

dbscSNV1_RF

Benign

0.0040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over