chr17-28959404-C-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_178860.5(SEZ6):c.1840G>A(p.Gly614Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00295 in 1,613,950 control chromosomes in the GnomAD database, including 54 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 0.0023 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0030 ( 53 hom. )
Consequence
SEZ6
NM_178860.5 missense
NM_178860.5 missense
Scores
1
16
Clinical Significance
Conservation
PhyloP100: 3.43
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.006298989).
BP6
?
Variant 17-28959404-C-T is Benign according to our data. Variant chr17-28959404-C-T is described in ClinVar as [Benign]. Clinvar id is 790331.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-28959404-C-T is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0023 (350/152288) while in subpopulation SAS AF= 0.0184 (89/4828). AF 95% confidence interval is 0.0153. There are 1 homozygotes in gnomad4. There are 194 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEZ6 | NM_178860.5 | c.1840G>A | p.Gly614Ser | missense_variant | 9/17 | ENST00000317338.17 | |
LOC105371716 | XR_001752822.2 | n.1807+5996C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEZ6 | ENST00000317338.17 | c.1840G>A | p.Gly614Ser | missense_variant | 9/17 | 1 | NM_178860.5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00230 AC: 350AN: 152170Hom.: 2 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00474 AC: 1181AN: 249080Hom.: 17 AF XY: 0.00572 AC XY: 773AN XY: 135130
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GnomAD4 exome AF: 0.00301 AC: 4406AN: 1461662Hom.: 53 Cov.: 32 AF XY: 0.00360 AC XY: 2616AN XY: 727120
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ExAC
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627
Asia WGS
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3478
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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, 2018 | - - |
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
Uncertain
D
LIST_S2
Benign
T;T;T;T;T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;N;.;.
MutationTaster
Benign
D;D;D;D
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
0.30
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