rs200765195
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_020451.3(SELENON):c.732G>A(p.Pro244=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 1,613,664 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
SELENON
NM_020451.3 synonymous
NM_020451.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.82
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 Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
Variant 1-25808774-G-A is Benign according to our data. Variant chr1-25808774-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 261285.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=2}.
BP7
?
Synonymous conserved (PhyloP=-2.82 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SELENON | NM_020451.3 | c.732G>A | p.Pro244= | synonymous_variant | 5/13 | ENST00000361547.7 | |
SELENON | NM_206926.2 | c.630G>A | p.Pro210= | synonymous_variant | 4/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SELENON | ENST00000361547.7 | c.732G>A | p.Pro244= | synonymous_variant | 5/13 | 1 | NM_020451.3 | ||
SELENON | ENST00000374315.1 | c.630G>A | p.Pro210= | synonymous_variant | 4/12 | 5 | P1 | ||
SELENON | ENST00000354177.9 | c.630G>A | p.Pro210= | synonymous_variant | 4/12 | 5 | |||
SELENON | ENST00000494537.2 | c.630G>A | p.Pro210= | synonymous_variant, NMD_transcript_variant | 4/13 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152180Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000884 AC: 22AN: 249004Hom.: 0 AF XY: 0.0000739 AC XY: 10AN XY: 135248
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GnomAD4 exome AF: 0.000107 AC: 157AN: 1461484Hom.: 0 Cov.: 32 AF XY: 0.000116 AC XY: 84AN XY: 727052
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GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152180Hom.: 0 Cov.: 33 AF XY: 0.0000942 AC XY: 7AN XY: 74336
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
SEPN1-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Eichsfeld type congenital muscular dystrophy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 15, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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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