1-25814046-C-T
Position:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_020451.3(SELENON):c.1501-31C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00781 in 1,609,110 control chromosomes in the GnomAD database, including 643 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.037 ( 360 hom., cov: 32)
Exomes 𝑓: 0.0047 ( 283 hom. )
Consequence
SELENON
NM_020451.3 intron
NM_020451.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.190
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 1-25814046-C-T is Benign according to our data. Variant chr1-25814046-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 261276.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-25814046-C-T is described in Lovd as [Likely_benign]. Variant chr1-25814046-C-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SELENON | NM_020451.3 | c.1501-31C>T | intron_variant | ENST00000361547.7 | |||
SELENON | NM_206926.2 | c.1399-31C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SELENON | ENST00000361547.7 | c.1501-31C>T | intron_variant | 1 | NM_020451.3 | ||||
SELENON | ENST00000354177.9 | c.1330-31C>T | intron_variant | 5 | |||||
SELENON | ENST00000374315.1 | c.1399-31C>T | intron_variant | 5 | P1 | ||||
SELENON | ENST00000494537.2 | c.*21-31C>T | intron_variant, NMD_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0372 AC: 5652AN: 152112Hom.: 361 Cov.: 32
GnomAD3 genomes
AF:
AC:
5652
AN:
152112
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0117 AC: 2929AN: 249342Hom.: 139 AF XY: 0.00972 AC XY: 1315AN XY: 135292
GnomAD3 exomes
AF:
AC:
2929
AN:
249342
Hom.:
AF XY:
AC XY:
1315
AN XY:
135292
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00473 AC: 6896AN: 1456880Hom.: 283 Cov.: 29 AF XY: 0.00436 AC XY: 3159AN XY: 725086
GnomAD4 exome
AF:
AC:
6896
AN:
1456880
Hom.:
Cov.:
29
AF XY:
AC XY:
3159
AN XY:
725086
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0372 AC: 5664AN: 152230Hom.: 360 Cov.: 32 AF XY: 0.0356 AC XY: 2648AN XY: 74418
GnomAD4 genome
AF:
AC:
5664
AN:
152230
Hom.:
Cov.:
32
AF XY:
AC XY:
2648
AN XY:
74418
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
83
AN:
3478
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 16, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at