rs121908187

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM4PP5

The NM_020451.3(SELENON):​c.1384T>G​(p.Ter462Glyext*?) variant causes a stop lost change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. *462*) has been classified as Pathogenic.

Frequency

Genomes: not found (cov: 31)

Consequence

SELENON
NM_020451.3 stop_lost

Scores

1
4
7

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.98
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 Uncertain_significance. Variant got 5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM4
Stoplost variant in NM_020451.3 Downstream stopcodon found after 138 codons.
PP5
Variant 1-25812789-T-G is Pathogenic according to our data. Variant chr1-25812789-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 4495.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-25812789-T-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SELENONNM_020451.3 linkuse as main transcriptc.1384T>G p.Ter462Glyext*? stop_lost 10/13 ENST00000361547.7 NP_065184.2 Q9NZV5-1
SELENONNM_206926.2 linkuse as main transcriptc.1282T>G p.Ter428Glyext*? stop_lost 9/12 NP_996809.1 Q9NZV5-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SELENONENST00000361547.7 linkuse as main transcriptc.1384T>G p.Ter462Glyext*? stop_lost 10/131 NM_020451.3 ENSP00000355141.2 Q9NZV5-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Eichsfeld type congenital muscular dystrophy Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMOct 01, 2002- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
0.037
T
BayesDel_noAF
Benign
-0.18
CADD
Benign
20
DANN
Benign
0.91
DEOGEN2
Benign
0.046
T;.
Eigen
Uncertain
0.25
Eigen_PC
Uncertain
0.40
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.0
T;T
MetaRNN
Uncertain
0.52
D;D
PROVEAN
Benign
-0.12
N;N
Sift
Benign
0.54
T;T
MVP
0.84
GERP RS
5.6

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs121908187; hg19: chr1-26139280; API