rs753400008
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_020451.3(SELENON):c.979C>T(p.Arg327Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R327H) has been classified as Uncertain significance.
Frequency
Consequence
NM_020451.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SELENON | ENST00000361547.7 | c.979C>T | p.Arg327Cys | missense_variant | Exon 7 of 13 | 1 | NM_020451.3 | ENSP00000355141.2 | ||
SELENON | ENST00000374315.1 | c.877C>T | p.Arg293Cys | missense_variant | Exon 6 of 12 | 5 | ENSP00000363434.1 | |||
SELENON | ENST00000354177.9 | c.808C>T | p.Arg270Cys | missense_variant | Exon 6 of 12 | 5 | ENSP00000346109.5 | |||
SELENON | ENST00000494537.2 | n.877C>T | non_coding_transcript_exon_variant | Exon 6 of 13 | 3 | ENSP00000508308.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000802 AC: 2AN: 249426Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135360
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461686Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727154
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Eichsfeld type congenital muscular dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 19, 2025 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 327 of the SELENON protein (p.Arg327Cys). This variant is present in population databases (rs753400008, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with SELENON-related conditions. ClinVar contains an entry for this variant (Variation ID: 461636). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at