NM_020451.3:c.-14_-5dupCGCCAGCCGC

Variant names:

• chr1-25800209-G-GCAGCCGCCGC
• rs911788176
• NM_020451.3:c.-14_-5dupCGCCAGCCGC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_020451.3(SELENON):​c.-14_-5dupCGCCAGCCGC 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000048 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000097 (0 hom.)
• Consequence: SELENON NM_020451.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.206
• Publications: 0 publications found

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]

SELENON Gene-Disease associations (from GenCC):

• rigid spine muscular dystrophy 1

  Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics, G2P
• SELENON-related myopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• congenital myopathy 4A, autosomal dominant

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• congenital fiber-type disproportion myopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• desmin-related myopathy with Mallory body-like inclusions

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• rigid spine syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELENON	NM_020451.3	c.-14_-5dupCGCCAGCCGC		5_prime_UTR_variant	Exon 1 of 13	ENST00000361547.7	NP_065184.2
SELENON	NM_206926.2	c.-14_-5dupCGCCAGCCGC		5_prime_UTR_variant	Exon 1 of 12		NP_996809.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELENON	ENST00000361547.7	c.-14_-5dupCGCCAGCCGC		5_prime_UTR_variant	Exon 1 of 13	1	NM_020451.3	ENSP00000355141.2
SELENON	ENST00000374315.1	c.-14_-5dupCGCCAGCCGC		5_prime_UTR_variant	Exon 1 of 12	5		ENSP00000363434.1
SELENON	ENST00000354177.9	c.-22_-21insCAGCCGCCGC		upstream_gene_variant		5		ENSP00000346109.5
SELENON	ENST00000494537.2	n.-22_-21insCAGCCGCCGC		upstream_gene_variant		3		ENSP00000508308.1

Frequencies

GnomAD3 genomes AF: 0.0000482 AC: 7 AN: 145180 Hom.: 0 Cov.: 30

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

African (AFR) AF: 0.00 AC: 0 AN: 7758

American (AMR) AF: 0.00 AC: 0 AN: 492

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2556

East Asian (EAS) AF: 0.00 AC: 0 AN: 1776

South Asian (SAS) AF: 0.00 AC: 0 AN: 8670

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 138

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 798

European-Non Finnish (NFE) AF: 0.0000106 AC: 4 AN: 377064

Other (OTH) AF: 0.00 AC: 0 AN: 13508

GnomAD4 genome AF: 0.0000482 AC: 7 AN: 145180 Hom.: 0 Cov.: 30 AF XY: 0.0000425 AC XY: 3 AN XY: 70556

African (AFR) AF: 0.0000740 AC: 3 AN: 40536

American (AMR) AF: 0.00 AC: 0 AN: 14642

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3376

East Asian (EAS) AF: 0.00 AC: 0 AN: 5064

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4776

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8174

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.0000459 AC: 3 AN: 65408

Other (OTH) AF: 0.00 AC: 0 AN: 2002

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SELENON: BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.21

Splicing

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

Other links and lift over

dbSNP: rs911788176; hg19: chr1-26126700;