rs587776597

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5

The NM_020451.3(SELENON):​c.1385G>A​(p.Ter462Ter) variant causes a splice region, stop retained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 31)

Consequence

SELENON
NM_020451.3 splice_region, stop_retained

Scores

1
1
3
Splicing: ADA: 0.9239
2

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 9.95
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-25812790-G-A is Pathogenic according to our data. Variant chr1-25812790-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 4490.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-25812790-G-A 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.1385G>A p.Ter462Ter splice_region_variant, stop_retained_variant 10/13 ENST00000361547.7 NP_065184.2 Q9NZV5-1
SELENONNM_206926.2 linkuse as main transcriptc.1283G>A p.Ter428Ter splice_region_variant, stop_retained_variant 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.1385G>A p.Ter462Ter splice_region_variant, stop_retained_variant 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 onlyOMIMSep 01, 2001- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
0.069
T
BayesDel_noAF
Benign
-0.14
CADD
Pathogenic
48
DANN
Benign
0.93
FATHMM_MKL
Pathogenic
0.99
D
GERP RS
5.6

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.92
dbscSNV1_RF
Benign
0.72
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: rs587776597; hg19: chr1-26139281; API