chr17-28959135-C-T
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_178860.5(SEZ6):c.1997G>A(p.Arg666His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000809 in 1,613,832 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0039 ( 4 hom., cov: 32)
Exomes 𝑓: 0.00049 ( 2 hom. )
Consequence
SEZ6
NM_178860.5 missense
NM_178860.5 missense
Scores
17
Clinical Significance
Conservation
PhyloP100: -0.148
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 Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0036476552).
BP6
?
Variant 17-28959135-C-T is Benign according to our data. Variant chr17-28959135-C-T is described in ClinVar as [Benign]. Clinvar id is 768863.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High Homozygotes in GnomAd at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEZ6 | NM_178860.5 | c.1997G>A | p.Arg666His | missense_variant | 10/17 | ENST00000317338.17 | |
LOC105371716 | XR_001752822.2 | n.1807+5727C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEZ6 | ENST00000317338.17 | c.1997G>A | p.Arg666His | missense_variant | 10/17 | 1 | NM_178860.5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00388 AC: 591AN: 152212Hom.: 4 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00116 AC: 288AN: 248246Hom.: 1 AF XY: 0.00107 AC XY: 144AN XY: 134814
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GnomAD4 exome AF: 0.000490 AC: 716AN: 1461502Hom.: 2 Cov.: 32 AF XY: 0.000486 AC XY: 353AN XY: 727046
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GnomAD4 genome ? AF: 0.00387 AC: 590AN: 152330Hom.: 4 Cov.: 32 AF XY: 0.00358 AC XY: 267AN XY: 74480
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T;T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;L;.;.
MutationTaster
Benign
D;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;.;.;.;N
REVEL
Benign
Sift
Benign
T;.;.;.;T
Sift4G
Benign
T;T;T;T;T
Polyphen
B;.;B;.;.
Vest4
MVP
MPC
0.35
ClinPred
T
GERP RS
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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