1-43450971-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365999.1(SZT2):c.*491T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 762,158 control chromosomes in the GnomAD database, including 137,095 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 0.63 (30113 hom., cov: 30)
  • Exomes 𝑓: 0.59 (106982 hom.)
• Consequence: SZT2 NM_001365999.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.304

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]

HYI (HGNC:26948): (hydroxypyruvate isomerase (putative)) This gene encodes a putative hydroxypyruvate isomerase, which likely catalyzes the conversion of hydroxypyruvate to 2-hydroxy-3-oxopropanoate, and may be involved in carbohydrate transport and metabolism. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SZT2	NM_001365999.1	c.*491T>C		3_prime_UTR_variant	72/72	ENST00000634258.3
HYI	NM_001190880.3			downstream_gene_variant		ENST00000372430.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SZT2	ENST00000634258.3	c.*491T>C		3_prime_UTR_variant	72/72	5	NM_001365999.1	P1
HYI	ENST00000372430.9			downstream_gene_variant		1	NM_001190880.3	P1

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95183 AN: 151804 Hom.: 30071 Cov.: 30

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.640

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.646

GnomAD3 exomes AF: 0.588 AC: 135053 AN: 229612 Hom.: 40060 AF XY: 0.585 AC XY: 74228 AN XY: 126876

Gnomad AFR exome AF: 0.691

Gnomad AMR exome AF: 0.572

Gnomad ASJ exome AF: 0.649

Gnomad EAS exome AF: 0.539

Gnomad SAS exome AF: 0.485

Gnomad FIN exome AF: 0.626

Gnomad NFE exome AF: 0.607

Gnomad OTH exome AF: 0.595

GnomAD4 exome AF: 0.590 AC: 359919 AN: 610236 Hom.: 106982 Cov.: 3 AF XY: 0.584 AC XY: 195018 AN XY: 333702

Gnomad4 AFR exome AF: 0.687

Gnomad4 AMR exome AF: 0.578

Gnomad4 ASJ exome AF: 0.642

Gnomad4 EAS exome AF: 0.496

Gnomad4 SAS exome AF: 0.490

Gnomad4 FIN exome AF: 0.611

Gnomad4 NFE exome AF: 0.608

Gnomad4 OTH exome AF: 0.603

GnomAD4 genome AF: 0.627 AC: 95291 AN: 151922 Hom.: 30113 Cov.: 30 AF XY: 0.625 AC XY: 46368 AN XY: 74222

Gnomad4 AFR AF: 0.694

Gnomad4 AMR AF: 0.613

Gnomad4 ASJ AF: 0.638

Gnomad4 EAS AF: 0.523

Gnomad4 SAS AF: 0.490

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.607

Gnomad4 OTH AF: 0.648

Alfa AF: 0.599 Hom.: 19009

Bravo AF: 0.632

Asia WGS AF: 0.510 AC: 1773 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.72
Dann	Benign	0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs6954; hg19: chr1-43916642;