chr1-25800209-G-GCAGCCGCCGC
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP6_Moderate
The NM_020451.3(SELENON):c.-14_-5dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 557,940 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000048 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0000097 ( 0 hom. )
Consequence
SELENON
NM_020451.3 5_prime_UTR
NM_020451.3 5_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.206
Genes affected
SELENON (HGNC:15999): (selenoprotein N) This gene encodes a glycoprotein that is localized in the endoplasmic reticulum. It plays an important role in cell protection against oxidative stress, and in the regulation of redox-related calcium homeostasis. Mutations in this gene are associated with early onset muscle disorders, referred to as SEPN1-related myopathy. SEPN1-related myopathy consists of 4 autosomal recessive disorders, originally thought to be separate entities: rigid spine muscular dystrophy (RSMD1), the classical form of multiminicore disease, desmin related myopathy with Mallory-body like inclusions, and congenital fiber-type disproportion (CFTD). This protein is a selenoprotein, containing the rare amino acid selenocysteine (Sec). Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. A second stop-codon redefinition element (SRE) adjacent to the UGA codon has been identified in this gene (PMID:15791204). SRE is a phylogenetically conserved stem-loop structure that stimulates readthrough at the UGA codon, and augments the Sec insertion efficiency by SECIS. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 1-25800209-G-GCAGCCGCCGC is Benign according to our data. Variant chr1-25800209-G-GCAGCCGCCGC is described in ClinVar as [Likely_benign]. Clinvar id is 2638502.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SELENON | NM_020451.3 | c.-14_-5dup | 5_prime_UTR_variant | 1/13 | ENST00000361547.7 | ||
SELENON | NM_206926.2 | c.-14_-5dup | 5_prime_UTR_variant | 1/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SELENON | ENST00000361547.7 | c.-14_-5dup | 5_prime_UTR_variant | 1/13 | 1 | NM_020451.3 | |||
SELENON | ENST00000374315.1 | c.-14_-5dup | 5_prime_UTR_variant | 1/12 | 5 | P1 | |||
SELENON | ENST00000354177.9 | upstream_gene_variant | 5 | ||||||
SELENON | ENST00000494537.2 | upstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000482 AC: 7AN: 145180Hom.: 0 Cov.: 30
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GnomAD4 exome AF: 0.00000969 AC: 4AN: 412760Hom.: 0 Cov.: 6 AF XY: 0.00000517 AC XY: 1AN XY: 193372
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GnomAD4 genome AF: 0.0000482 AC: 7AN: 145180Hom.: 0 Cov.: 30 AF XY: 0.0000425 AC XY: 3AN XY: 70556
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2022 | SELENON: BP4 - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at