17-28956432-C-T
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_178860.5(SEZ6):c.2767G>A(p.Ala923Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000212 in 1,562,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00019 ( 0 hom. )
Consequence
SEZ6
NM_178860.5 missense
NM_178860.5 missense
Scores
7
12
Clinical Significance
Conservation
PhyloP100: 3.67
Genes affected
SEZ6 (HGNC:15955): (seizure related 6 homolog) The protein encoded by this gene is thought to contain five cysteine-rich motifs that are similar to sushi domains, as well as two domains similar to the amino terminal half of the CUB (for complement C1r/C1s, Uegf, Bmp1) domain. Mutations in this gene have been associated with febrile seizures. [provided by RefSeq, Jul 2016]
PIPOX (HGNC:17804): (pipecolic acid and sarcosine oxidase) Enables L-pipecolate oxidase activity and sarcosine oxidase activity. Involved in L-lysine catabolic process to acetyl-CoA via L-pipecolate. Located in peroxisome. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.046560585).
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000394 AC: 60AN: 152184Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000129 AC: 22AN: 171016Hom.: 0 AF XY: 0.0000992 AC XY: 9AN XY: 90724
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GnomAD4 exome AF: 0.000193 AC: 272AN: 1410346Hom.: 0 Cov.: 33 AF XY: 0.000207 AC XY: 144AN XY: 696658
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GnomAD4 genome AF: 0.000394 AC: 60AN: 152302Hom.: 0 Cov.: 32 AF XY: 0.000537 AC XY: 40AN XY: 74468
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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 | Dec 13, 2022 | The c.2767G>A (p.A923T) alteration is located in exon 15 (coding exon 15) of the SEZ6 gene. This alteration results from a G to A substitution at nucleotide position 2767, causing the alanine (A) at amino acid position 923 to be replaced by a threonine (T). 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
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T;T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;M;.;.
PrimateAI
Benign
T
PROVEAN
Benign
N;.;.;.;.
REVEL
Benign
Sift
Uncertain
D;.;.;.;.
Sift4G
Benign
T;T;T;T;T
Polyphen
B;.;B;.;.
Vest4
MVP
MPC
0.27
ClinPred
T
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