1-43389985-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001365999.1(SZT2):​c.17C>T​(p.Pro6Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000161 in 1,241,702 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P6R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

SZT2
NM_001365999.1 missense

Scores

7
12

Clinical Significance

Not reported in ClinVar

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]
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]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2669578).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SZT2NM_001365999.1 linkc.17C>T p.Pro6Leu missense_variant Exon 1 of 72 ENST00000634258.3 NP_001352928.1
MED8NM_201542.5 linkc.-221G>A upstream_gene_variant ENST00000372457.9 NP_963836.2 Q96G25-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SZT2ENST00000634258.3 linkc.17C>T p.Pro6Leu missense_variant Exon 1 of 72 5 NM_001365999.1 ENSP00000489255.1 Q5T011-1
MED8ENST00000372457.9 linkc.-221G>A upstream_gene_variant 2 NM_201542.5 ENSP00000361535.4 Q96G25-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000161
AC:
2
AN:
1241702
Hom.:
0
Cov.:
34
AF XY:
0.00000166
AC XY:
1
AN XY:
601476
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
24874
American (AMR)
AF:
0.00
AC:
0
AN:
13746
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
17764
East Asian (EAS)
AF:
0.0000344
AC:
1
AN:
29096
South Asian (SAS)
AF:
0.00
AC:
0
AN:
60350
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
30786
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4726
European-Non Finnish (NFE)
AF:
9.91e-7
AC:
1
AN:
1008890
Other (OTH)
AF:
0.00
AC:
0
AN:
51470
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Uncertain
0.012
T
BayesDel_noAF
Benign
-0.22
CADD
Pathogenic
26
DANN
Benign
0.96
DEOGEN2
Benign
0.068
.;T;.
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.77
T;T;T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.27
T;T;T
MetaSVM
Benign
-0.74
T
MutationAssessor
Benign
1.6
L;L;L
PhyloP100
3.4
PrimateAI
Uncertain
0.72
T
PROVEAN
Uncertain
-2.6
D;.;N
REVEL
Benign
0.23
Sift
Benign
0.12
T;.;T
Sift4G
Uncertain
0.059
T;D;D
Polyphen
1.0
D;.;.
Vest4
0.45
MutPred
0.40
Loss of glycosylation at P6 (P = 0.0218);Loss of glycosylation at P6 (P = 0.0218);Loss of glycosylation at P6 (P = 0.0218);
MVP
0.34
MPC
0.54
ClinPred
0.95
D
GERP RS
4.3
PromoterAI
-0.065
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.22
gMVP
0.19
Mutation Taster
=80/20
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

Publications

Other links and lift over

dbSNP: rs759762015; hg19: chr1-43855656; API