1-43450971-T-C

Variant names:

• chr1-43450971-T-C
• rs6954
• NM_001365999.1:c.*491T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 29 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]

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

Our verdict: Benign. The variant received -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.

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.*491T>C		3_prime_UTR	Exon 72 of 72	NP_001352928.1	Q5T011-1
	SZT2	NM_015284.4		c.*491T>C		3_prime_UTR	Exon 71 of 71	NP_056099.3	Q5T011-5
	HYI	NM_001190880.3	MANE Select	c.*267A>G		downstream_gene	N/A	NP_001177809.1	Q5T013-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SZT2	ENST00000634258.3	TSL:5 MANE Select	c.*491T>C		3_prime_UTR	Exon 72 of 72	ENSP00000489255.1	Q5T011-1
	SZT2	ENST00000562955.2	TSL:5	c.*491T>C		3_prime_UTR	Exon 71 of 71	ENSP00000457168.1	Q5T011-5
	HYI	ENST00000895723.1		c.*267A>G		3_prime_UTR	Exon 8 of 8	ENSP00000565782.1

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

GnomAD2 exomes AF: 0.588 AC: 135053 AN: 229612 AF XY: 0.585

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 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

African (AFR) AF: 0.687 AC: 12126 AN: 17650

American (AMR) AF: 0.578 AC: 25255 AN: 43670

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 13430 AN: 20922

East Asian (EAS) AF: 0.496 AC: 17803 AN: 35886

South Asian (SAS) AF: 0.490 AC: 33803 AN: 68942

European-Finnish (FIN) AF: 0.611 AC: 22839 AN: 37404

Middle Eastern (MID) AF: 0.645 AC: 2669 AN: 4136

European-Non Finnish (NFE) AF: 0.608 AC: 212199 AN: 348776

Other (OTH) AF: 0.603 AC: 19795 AN: 32850

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

African (AFR) AF: 0.694 AC: 28720 AN: 41408

American (AMR) AF: 0.613 AC: 9367 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 2213 AN: 3466

East Asian (EAS) AF: 0.523 AC: 2688 AN: 5138

South Asian (SAS) AF: 0.490 AC: 2357 AN: 4814

European-Finnish (FIN) AF: 0.628 AC: 6635 AN: 10572

Middle Eastern (MID) AF: 0.651 AC: 190 AN: 292

European-Non Finnish (NFE) AF: 0.607 AC: 41225 AN: 67934

Other (OTH) AF: 0.648 AC: 1369 AN: 2114

Alfa AF: 0.607 Hom.: 34909

Bravo AF: 0.632

Asia WGS AF: 0.510 AC: 1773 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.72
DANN	Benign	0.38
PhyloP100		-0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6954; hg19: chr1-43916642; COSMIC: COSV107469174; COSMIC: COSV107469174;