rs187880136

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

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.33
Variant links:
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 -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
SELENONNM_020451.3 linkuse as main transcriptc.852C>T p.Phe284Phe synonymous_variant 6/13 ENST00000361547.7 NP_065184.2 Q9NZV5-1
SELENONNM_206926.2 linkuse as main transcriptc.750C>T p.Phe250Phe synonymous_variant 5/12 NP_996809.1 Q9NZV5-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SELENONENST00000361547.7 linkuse as main transcriptc.852C>T p.Phe284Phe synonymous_variant 6/131 NM_020451.3 ENSP00000355141.2 Q9NZV5-1
SELENONENST00000374315.1 linkuse as main transcriptc.750C>T p.Phe250Phe synonymous_variant 5/125 ENSP00000363434.1 Q9NZV5-2
SELENONENST00000354177.9 linkuse as main transcriptc.681C>T p.Phe227Phe synonymous_variant 5/125 ENSP00000346109.5 H9KV50
SELENONENST00000494537.2 linkuse as main transcriptn.750C>T non_coding_transcript_exon_variant 5/133 ENSP00000508308.1 A0A804HLD6

Frequencies

GnomAD3 genomes
AF:
0.00130
AC:
198
AN:
152250
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00453
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000589
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000333
AC:
83
AN:
249268
Hom.:
0
AF XY:
0.000273
AC XY:
37
AN XY:
135370
show subpopulations
Gnomad AFR exome
AF:
0.00492
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000884
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.000114
AC:
166
AN:
1461424
Hom.:
1
Cov.:
33
AF XY:
0.0000977
AC XY:
71
AN XY:
727024
show subpopulations
Gnomad4 AFR exome
AF:
0.00418
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.000248
GnomAD4 genome
AF:
0.00130
AC:
198
AN:
152368
Hom.:
1
Cov.:
33
AF XY:
0.00129
AC XY:
96
AN XY:
74504
show subpopulations
Gnomad4 AFR
AF:
0.00452
Gnomad4 AMR
AF:
0.000588
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.00106
Hom.:
0
Bravo
AF:
0.00125
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 submitterclinical testingCeGaT Center for Human Genetics TuebingenDec 01, 2023SELENON: BP4 -
Likely benign, criteria provided, single submitterclinical testingGeneDxJan 30, 2020- -
Likely benign, criteria provided, single submitterclinical testingAthena DiagnosticsDec 21, 2017- -
SELENON-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesJul 19, 2019This 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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 04, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.28
CADD
Benign
14
DANN
Benign
0.87

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs187880136; hg19: chr1-26135621; API