chr1-43450971-T-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001365999.1(SZT2):​c.*491T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000164 in 610,468 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0000016 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SZT2	NM_001365999.1	MANE Select	c.*491T>A		3_prime_UTR	Exon 72 of 72	NP_001352928.1
	SZT2	NM_015284.4		c.*491T>A		3_prime_UTR	Exon 71 of 71	NP_056099.3
	HYI	NM_001190880.3	MANE Select	c.*267A>T		downstream_gene	N/A	NP_001177809.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SZT2	ENST00000634258.3	TSL:5 MANE Select	c.*491T>A		3_prime_UTR	Exon 72 of 72	ENSP00000489255.1
	SZT2	ENST00000460536.1	TSL:2	n.2607T>A		non_coding_transcript_exon	Exon 10 of 10
	SZT2	ENST00000638263.1	TSL:5	n.4138T>A		non_coding_transcript_exon	Exon 8 of 8

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000164 AC: 1 AN: 610468 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 333824

African (AFR) AF: 0.00 AC: 0 AN: 17654

American (AMR) AF: 0.00 AC: 0 AN: 43674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20930

East Asian (EAS) AF: 0.00 AC: 0 AN: 35908

South Asian (SAS) AF: 0.00 AC: 0 AN: 68944

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37432

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 348930

Other (OTH) AF: 0.0000304 AC: 1 AN: 32860

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.59
DANN	Benign	0.52
PhyloP100		-0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs6954; hg19: chr1-43916642;