chr1-25800209-G-GCAGCCGCCGC

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP6_Moderate

The NM_020451.3(SELENON):​c.-14_-5dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 557,940 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000048 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0000097 ( 0 hom. )

Consequence

SELENON
NM_020451.3 5_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.206
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 1-25800209-G-GCAGCCGCCGC is Benign according to our data. Variant chr1-25800209-G-GCAGCCGCCGC is described in ClinVar as [Likely_benign]. Clinvar id is 2638502.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SELENONNM_020451.3 linkuse as main transcriptc.-14_-5dup 5_prime_UTR_variant 1/13 ENST00000361547.7
SELENONNM_206926.2 linkuse as main transcriptc.-14_-5dup 5_prime_UTR_variant 1/12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SELENONENST00000361547.7 linkuse as main transcriptc.-14_-5dup 5_prime_UTR_variant 1/131 NM_020451.3 Q9NZV5-1
SELENONENST00000374315.1 linkuse as main transcriptc.-14_-5dup 5_prime_UTR_variant 1/125 P1Q9NZV5-2
SELENONENST00000354177.9 linkuse as main transcript upstream_gene_variant 5
SELENONENST00000494537.2 linkuse as main transcript upstream_gene_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0000482
AC:
7
AN:
145180
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0000740
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000209
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000459
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000969
AC:
4
AN:
412760
Hom.:
0
Cov.:
6
AF XY:
0.00000517
AC XY:
1
AN XY:
193372
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000106
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000482
AC:
7
AN:
145180
Hom.:
0
Cov.:
30
AF XY:
0.0000425
AC XY:
3
AN XY:
70556
show subpopulations
Gnomad4 AFR
AF:
0.0000740
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000209
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000459
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenSep 01, 2022SELENON: BP4 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs911788176; hg19: chr1-26126700; API