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 rank MANE Protein UniProt
SELENONNM_020451.3 linkc.852C>T p.Phe284Phe synonymous_variant Exon 6 of 13 ENST00000361547.7 NP_065184.2 Q9NZV5-1
SELENONNM_206926.2 linkc.750C>T p.Phe250Phe synonymous_variant Exon 5 of 12 NP_996809.1 Q9NZV5-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SELENONENST00000361547.7 linkc.852C>T p.Phe284Phe synonymous_variant Exon 6 of 13 1 NM_020451.3 ENSP00000355141.2 Q9NZV5-1
SELENONENST00000374315.1 linkc.750C>T p.Phe250Phe synonymous_variant Exon 5 of 12 5 ENSP00000363434.1 Q9NZV5-2
SELENONENST00000354177.9 linkc.681C>T p.Phe227Phe synonymous_variant Exon 5 of 12 5 ENSP00000346109.5 H9KV50
SELENONENST00000494537.2 linkn.750C>T non_coding_transcript_exon_variant Exon 5 of 13 3 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 testingGeneDxJan 30, 2020- -
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenDec 01, 2023SELENON: BP4 -
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), LabcorpDec 26, 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