rs780157180

Variant names:

• chr1-43420759-A-C
• NM_001365999.1:c.1272A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-43420759-A-C
• chr1-43420759-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001365999.1(SZT2):​c.1272A>C​(p.Gln424His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,446,116 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. Synonymous variant affecting the same amino acid position (i.e. Q424Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SZT2 NM_001365999.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.35

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2436032).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SZT2	NM_001365999.1	c.1272A>C	p.Gln424His	missense_variant	Exon 10 of 72	ENST00000634258.3	NP_001352928.1
SZT2	NM_015284.4	c.1272A>C	p.Gln424His	missense_variant	Exon 10 of 71		NP_056099.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SZT2	ENST00000634258.3	c.1272A>C	p.Gln424His	missense_variant	Exon 10 of 72	5	NM_001365999.1	ENSP00000489255.1
SZT2	ENST00000562955.2	c.1272A>C	p.Gln424His	missense_variant	Exon 10 of 71	5		ENSP00000457168.1
SZT2	ENST00000470139.1	n.3A>C		non_coding_transcript_exon_variant	Exon 1 of 18	2		ENSP00000492726.1
SZT2	ENST00000639852.1	n.938A>C		non_coding_transcript_exon_variant	Exon 7 of 9	5		ENSP00000492385.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1446116 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 719770

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.092	T;.
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.81	T;T
M_CAP	Pathogenic	0.42	D
MetaRNN	Benign	0.24	T;T
MutationAssessor	Benign	1.6	L;L
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.2	.;N
Sift	Uncertain	0.020	.;D
Sift4G	Benign	0.21	T;T
Vest4		0.33
MVP		0.45
MPC		1.4
GERP RS		-0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.046
gMVP		0.90

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-43886430;