chr22-26293134-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_021115.5(SEZ6L):c.823G>A(p.Glu275Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000839 in 1,549,518 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000072 ( 0 hom. )
Consequence
SEZ6L
NM_021115.5 missense
NM_021115.5 missense
Scores
1
6
11
Clinical Significance
Conservation
PhyloP100: 5.85
Genes affected
SEZ6L (HGNC:10763): (seizure related 6 homolog like) Predicted to act upstream of or within adult locomotory behavior; nervous system development; and regulation of protein kinase C signaling. Predicted to be located in endoplasmic reticulum and neuronal cell body. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEZ6L | NM_021115.5 | c.823G>A | p.Glu275Lys | missense_variant | 2/17 | ENST00000248933.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEZ6L | ENST00000248933.11 | c.823G>A | p.Glu275Lys | missense_variant | 2/17 | 1 | NM_021115.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152086Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000190 AC: 3AN: 158104Hom.: 0 AF XY: 0.0000235 AC XY: 2AN XY: 85280
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GnomAD4 exome AF: 0.00000716 AC: 10AN: 1397314Hom.: 0 Cov.: 33 AF XY: 0.0000101 AC XY: 7AN XY: 692312
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74414
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 12, 2023 | The c.823G>A (p.E275K) alteration is located in exon 2 (coding exon 2) of the SEZ6L gene. This alteration results from a G to A substitution at nucleotide position 823, causing the glutamic acid (E) at amino acid position 275 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;L;L;L;L;.;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;.;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;.;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T;T;T
Polyphen
0.98, 1.0, 0.99, 1.0
.;D;D;.;D;D;D;.
Vest4
MutPred
Gain of methylation at E275 (P = 0.0024);Gain of methylation at E275 (P = 0.0024);Gain of methylation at E275 (P = 0.0024);Gain of methylation at E275 (P = 0.0024);Gain of methylation at E275 (P = 0.0024);Gain of methylation at E275 (P = 0.0024);.;.;
MVP
MPC
0.40
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at