NM_020451.3:c.-30_64delGGCCGCCGGCAGCCGCCGCCAGCCGCAGCCATGGGCCGGGCCCGGCCGGGCCAACGCGGGCCGCCCAGCCCCGGCCCCGCCGCGCAGCCTCCCG
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PS1_ModeratePP5_Moderate
The NM_020451.3(SELENON):c.-30_64delGGCCGCCGGCAGCCGCCGCCAGCCGCAGCCATGGGCCGGGCCCGGCCGGGCCAACGCGGGCCGCCCAGCCCCGGCCCCGCCGCGCAGCCTCCCG(p.Met1fs) variant causes a frameshift, start lost change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000043 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SELENON
NM_020451.3 frameshift, start_lost
NM_020451.3 frameshift, start_lost
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.881
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 1Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P, Ambry Genetics
- SELENON-related myopathyInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- congenital myopathy 4A, autosomal dominantInheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- congenital fiber-type disproportion myopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- desmin-related myopathy with Mallory body-like inclusionsInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- rigid spine syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 93 pathogenic variants in the truncated region.
PS1
Another start lost variant in NM_020451.3 (SELENON) was described as [Likely_pathogenic] in ClinVar
PP5
Variant 1-25800195-TTCCCGGGCCGCCGGCAGCCGCCGCCAGCCGCAGCCATGGGCCGGGCCCGGCCGGGCCAACGCGGGCCGCCCAGCCCCGGCCCCGCCGCGCAGCC-T is Pathogenic according to our data. Variant chr1-25800195-TTCCCGGGCCGCCGGCAGCCGCCGCCAGCCGCAGCCATGGGCCGGGCCCGGCCGGGCCAACGCGGGCCGCCCAGCCCCGGCCCCGCCGCGCAGCC-T is described in ClinVar as Pathogenic. ClinVar VariationId is 2418838.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_020451.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SELENON | MANE Select | c.-30_64delGGCCGCCGGCAGCCGCCGCCAGCCGCAGCCATGGGCCGGGCCCGGCCGGGCCAACGCGGGCCGCCCAGCCCCGGCCCCGCCGCGCAGCCTCCCG | p.Met1fs | frameshift start_lost | Exon 1 of 13 | NP_065184.2 | |||
| SELENON | MANE Select | c.-30_64delGGCCGCCGGCAGCCGCCGCCAGCCGCAGCCATGGGCCGGGCCCGGCCGGGCCAACGCGGGCCGCCCAGCCCCGGCCCCGCCGCGCAGCCTCCCG | 5_prime_UTR | Exon 1 of 13 | NP_065184.2 | ||||
| SELENON | c.-30_64delGGCCGCCGGCAGCCGCCGCCAGCCGCAGCCATGGGCCGGGCCCGGCCGGGCCAACGCGGGCCGCCCAGCCCCGGCCCCGCCGCGCAGCCTCCCG | p.Met1fs | frameshift start_lost | Exon 1 of 12 | NP_996809.1 | Q9NZV5-2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SELENON | TSL:1 MANE Select | c.-30_64delGGCCGCCGGCAGCCGCCGCCAGCCGCAGCCATGGGCCGGGCCCGGCCGGGCCAACGCGGGCCGCCCAGCCCCGGCCCCGCCGCGCAGCCTCCCG | p.Met1fs | frameshift start_lost | Exon 1 of 13 | ENSP00000355141.2 | Q9NZV5-1 | ||
| SELENON | TSL:1 MANE Select | c.-30_64delGGCCGCCGGCAGCCGCCGCCAGCCGCAGCCATGGGCCGGGCCCGGCCGGGCCAACGCGGGCCGCCCAGCCCCGGCCCCGCCGCGCAGCCTCCCG | 5_prime_UTR | Exon 1 of 13 | ENSP00000355141.2 | Q9NZV5-1 | |||
| SELENON | TSL:5 | c.-30_64delGGCCGCCGGCAGCCGCCGCCAGCCGCAGCCATGGGCCGGGCCCGGCCGGGCCAACGCGGGCCGCCCAGCCCCGGCCCCGCCGCGCAGCCTCCCG | p.Met1fs | frameshift start_lost | Exon 1 of 12 | ENSP00000363434.1 | Q9NZV5-2 |
Frequencies
GnomAD3 genomes 0.00 AC: 0AN: 142028Hom.: 0 Cov.: 30
GnomAD3 genomes
AF:
AC:
0
AN:
142028
Hom.:
Cov.:
30
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
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Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
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Gnomad FIN
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Gnomad MID
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Gnomad NFE
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Gnomad OTH
AF:
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000434 AC: 8AN: 184158Hom.: 0 AF XY: 0.0000575 AC XY: 5AN XY: 86910 show subpopulations
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
8
AN:
184158
Hom.:
AF XY:
AC XY:
5
AN XY:
86910
show subpopulations
African (AFR)
AF:
AC:
0
AN:
3598
American (AMR)
AF:
AC:
0
AN:
210
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
1062
East Asian (EAS)
AF:
AC:
0
AN:
774
South Asian (SAS)
AF:
AC:
0
AN:
3972
European-Finnish (FIN)
AF:
AC:
0
AN:
62
Middle Eastern (MID)
AF:
AC:
0
AN:
334
European-Non Finnish (NFE)
AF:
AC:
8
AN:
168050
Other (OTH)
AF:
AC:
0
AN:
6096
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.463
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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2
4
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<30
30-35
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Age
GnomAD4 genome 0.00 AC: 0AN: 142028Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 68888
GnomAD4 genome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
AC:
0
AN:
142028
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
68888
African (AFR)
AF:
AC:
0
AN:
39386
American (AMR)
AF:
AC:
0
AN:
14496
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3334
East Asian (EAS)
AF:
AC:
0
AN:
4894
South Asian (SAS)
AF:
AC:
0
AN:
4646
European-Finnish (FIN)
AF:
AC:
0
AN:
7724
Middle Eastern (MID)
AF:
AC:
0
AN:
296
European-Non Finnish (NFE)
AF:
AC:
0
AN:
64386
Other (OTH)
AF:
AC:
0
AN:
1990
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Eichsfeld type congenital muscular dystrophy (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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