1-25800195-TTCCCGGGCCGCCGGCAGCCGCCGCCAGCCGCAGCCATGGGCCGGGCCCGGCCGGGCCAACGCGGGCCGCCCAGCCCCGGCCCCGCCGCGCAGCC-T
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
Consequence
NM_020451.3 frameshift, start_lost
Scores
Clinical Significance
Conservation
Publications
- rigid spine muscular dystrophy 1Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics, G2P
- 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
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ACMG classification
Our verdict: Pathogenic. The variant received 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SELENON | NM_020451.3 | c.-30_64delGGCCGCCGGCAGCCGCCGCCAGCCGCAGCCATGGGCCGGGCCCGGCCGGGCCAACGCGGGCCGCCCAGCCCCGGCCCCGCCGCGCAGCCTCCCG | p.Met1fs | frameshift_variant, start_lost | Exon 1 of 13 | ENST00000361547.7 | NP_065184.2 | |
SELENON | NM_020451.3 | c.-30_64delGGCCGCCGGCAGCCGCCGCCAGCCGCAGCCATGGGCCGGGCCCGGCCGGGCCAACGCGGGCCGCCCAGCCCCGGCCCCGCCGCGCAGCCTCCCG | 5_prime_UTR_variant | Exon 1 of 13 | ENST00000361547.7 | NP_065184.2 | ||
SELENON | NM_206926.2 | c.-30_64delGGCCGCCGGCAGCCGCCGCCAGCCGCAGCCATGGGCCGGGCCCGGCCGGGCCAACGCGGGCCGCCCAGCCCCGGCCCCGCCGCGCAGCCTCCCG | p.Met1fs | frameshift_variant, start_lost | Exon 1 of 12 | NP_996809.1 | ||
SELENON | NM_206926.2 | c.-30_64delGGCCGCCGGCAGCCGCCGCCAGCCGCAGCCATGGGCCGGGCCCGGCCGGGCCAACGCGGGCCGCCCAGCCCCGGCCCCGCCGCGCAGCCTCCCG | 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.-30_64delGGCCGCCGGCAGCCGCCGCCAGCCGCAGCCATGGGCCGGGCCCGGCCGGGCCAACGCGGGCCGCCCAGCCCCGGCCCCGCCGCGCAGCCTCCCG | p.Met1fs | frameshift_variant, start_lost | Exon 1 of 13 | 1 | NM_020451.3 | ENSP00000355141.2 | ||
SELENON | ENST00000361547.7 | c.-30_64delGGCCGCCGGCAGCCGCCGCCAGCCGCAGCCATGGGCCGGGCCCGGCCGGGCCAACGCGGGCCGCCCAGCCCCGGCCCCGCCGCGCAGCCTCCCG | 5_prime_UTR_variant | Exon 1 of 13 | 1 | NM_020451.3 | ENSP00000355141.2 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 0AN: 142028Hom.: 0 Cov.: 30
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 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 142028Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 68888
ClinVar
Submissions by phenotype
Eichsfeld type congenital muscular dystrophy Pathogenic:1
For these reasons, this variant has been classified as Pathogenic. This variant is also known as c.-34_60del. Disruption of the initiator codon has been observed in individuals with SELENON-related conditions (PMID: 12192640, 21670436, 23394784, 28558865). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the gnomAD database. This sequence change affects the initiator methionine of the SELENON mRNA. The next in-frame methionine is located at codon 85. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at