chr1-43389976-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001365999.1(SZT2):c.8C>T(p.Ser3Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000804 in 1,244,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S3A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 8.0e-7 ( 0 hom. )

Consequence

SZT2
NM_001365999.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.36

Publications

0 publications found

Variant links:

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]

SZT2 links:

MED8 (HGNC:19971): (mediator complex subunit 8) This gene encodes a protein component of the mediator complex, which aids in transcriptional activation through interaction with RNA polymerase II and gene-specific transcription factors. The encoded protein may also function in ubiquitin ligation and protein degradation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2013]

MED8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20121354).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SZT2	NM_001365999.1	MANE Select	c.8C>T	p.Ser3Leu	missense	Exon 1 of 72	NP_001352928.1	Q5T011-1
SZT2	NM_015284.4		c.8C>T	p.Ser3Leu	missense	Exon 1 of 71	NP_056099.3	Q5T011-5
MED8	NM_201542.5	MANE Select	c.-212G>A		upstream_gene	N/A	NP_963836.2	Q96G25-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SZT2	ENST00000634258.3	TSL:5 MANE Select	c.8C>T	p.Ser3Leu	missense	Exon 1 of 72	ENSP00000489255.1	Q5T011-1
SZT2	ENST00000372450.8	TSL:1	c.8C>T	p.Ser3Leu	missense	Exon 1 of 5	ENSP00000361528.4	Q5T011-7
SZT2	ENST00000357658.4	TSL:1	n.26C>T		non_coding_transcript_exon	Exon 1 of 5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.04e-7

AC:

AN:

1244406

Hom.:

Cov.:

AF XY:

0.00000166

AC XY:

AN XY:

603090

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25088

American (AMR)

AF:

0.00

AC:

AN:

14154

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17800

East Asian (EAS)

AF:

0.00

AC:

AN:

29250

South Asian (SAS)

AF:

0.0000164

AC:

AN:

60866

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31054

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4818

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1009768

Other (OTH)

AF:

0.00

AC:

AN:

51608

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.0036

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.019

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.0

PhyloP100

3.4

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.099

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.021

Polyphen

0.59

Vest4

0.46

MutPred

0.30

Loss of phosphorylation at S3 (P = 0.0032)

MVP

0.35

MPC

0.48

ClinPred

0.81

GERP RS

4.3

PromoterAI

-0.049

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.35

gMVP

0.19

Mutation Taster

=77/23

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over