1-43389907-G-C

Position:

• chr1-43389907-G-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001365999.1(SZT2):​c.-62G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 1,553,340 control chromosomes in the GnomAD database, including 327,454 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.66 (32991 hom., cov: 33)
  • Exomes 𝑓: 0.65 (294463 hom.)
• Consequence: SZT2 NM_001365999.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0970

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 1-43389907-G-C is Benign according to our data. Variant chr1-43389907-G-C is described in ClinVar as [Benign]. Clinvar id is 1252133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SZT2	NM_001365999.1	c.-62G>C		5_prime_UTR_variant	1/72	ENST00000634258.3	NP_001352928.1
SZT2	NM_015284.4	c.-62G>C		5_prime_UTR_variant	1/71		NP_056099.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SZT2	ENST00000634258.3	c.-62G>C		5_prime_UTR_variant	1/72	5	NM_001365999.1	ENSP00000489255	P1

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99789 AN: 152044 Hom.: 32950 Cov.: 33

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.658

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.687

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.673

GnomAD4 exome AF: 0.646 AC: 905338 AN: 1401178 Hom.: 294463 Cov.: 39 AF XY: 0.642 AC XY: 445031 AN XY: 693260

Gnomad4 AFR exome AF: 0.685

Gnomad4 AMR exome AF: 0.596

Gnomad4 ASJ exome AF: 0.662

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.496

Gnomad4 FIN exome AF: 0.680

Gnomad4 NFE exome AF: 0.661

Gnomad4 OTH exome AF: 0.646

GnomAD4 genome AF: 0.657 AC: 99898 AN: 152162 Hom.: 32991 Cov.: 33 AF XY: 0.654 AC XY: 48618 AN XY: 74394

Gnomad4 AFR AF: 0.686

Gnomad4 AMR AF: 0.642

Gnomad4 ASJ AF: 0.658

Gnomad4 EAS AF: 0.523

Gnomad4 SAS AF: 0.499

Gnomad4 FIN AF: 0.687

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.675

Alfa AF: 0.654 Hom.: 4066

Bravo AF: 0.658

Asia WGS AF: 0.518 AC: 1802 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	13
DANN	Benign	0.91

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs839753; hg19: chr1-43855578; COSMIC: COSV51941570; COSMIC: COSV51941570;