rs187880136
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS1
The NM_020451.3(SELENON):c.852C>T(p.Phe284Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000226 in 1,613,792 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0013 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00011 ( 1 hom. )
Consequence
SELENON
NM_020451.3 synonymous
NM_020451.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.33
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 Benign. Variant got -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.28).
BP6
Variant 1-25809130-C-T is Benign according to our data. Variant chr1-25809130-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 461635.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=2.33 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0013 (198/152368) while in subpopulation AFR AF= 0.00452 (188/41596). AF 95% confidence interval is 0.00399. There are 1 homozygotes in gnomad4. There are 96 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SELENON | NM_020451.3 | c.852C>T | p.Phe284Phe | synonymous_variant | 6/13 | ENST00000361547.7 | NP_065184.2 | |
SELENON | NM_206926.2 | c.750C>T | p.Phe250Phe | synonymous_variant | 5/12 | NP_996809.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SELENON | ENST00000361547.7 | c.852C>T | p.Phe284Phe | synonymous_variant | 6/13 | 1 | NM_020451.3 | ENSP00000355141.2 | ||
SELENON | ENST00000374315.1 | c.750C>T | p.Phe250Phe | synonymous_variant | 5/12 | 5 | ENSP00000363434.1 | |||
SELENON | ENST00000354177.9 | c.681C>T | p.Phe227Phe | synonymous_variant | 5/12 | 5 | ENSP00000346109.5 | |||
SELENON | ENST00000494537.2 | n.750C>T | non_coding_transcript_exon_variant | 5/13 | 3 | ENSP00000508308.1 |
Frequencies
GnomAD3 genomes AF: 0.00130 AC: 198AN: 152250Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.000333 AC: 83AN: 249268Hom.: 0 AF XY: 0.000273 AC XY: 37AN XY: 135370
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GnomAD4 exome AF: 0.000114 AC: 166AN: 1461424Hom.: 1 Cov.: 33 AF XY: 0.0000977 AC XY: 71AN XY: 727024
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GnomAD4 genome AF: 0.00130 AC: 198AN: 152368Hom.: 1 Cov.: 33 AF XY: 0.00129 AC XY: 96AN XY: 74504
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2023 | SELENON: BP4 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 30, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 21, 2017 | - - |
SELENON-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 19, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Eichsfeld type congenital muscular dystrophy Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 04, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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