rs199742668
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_020451.3(SELENON):c.550G>A(p.Ala184Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign 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. A184P) has been classified as Likely benign.
Frequency
Consequence
NM_020451.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SELENON | NM_020451.3 | c.550G>A | p.Ala184Thr | missense_variant | 5/13 | ENST00000361547.7 | |
SELENON | NM_206926.2 | c.448G>A | p.Ala150Thr | missense_variant | 4/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SELENON | ENST00000361547.7 | c.550G>A | p.Ala184Thr | missense_variant | 5/13 | 1 | NM_020451.3 | ||
SELENON | ENST00000374315.1 | c.448G>A | p.Ala150Thr | missense_variant | 4/12 | 5 | P1 | ||
SELENON | ENST00000354177.9 | c.448G>A | p.Ala150Thr | missense_variant | 4/12 | 5 | |||
SELENON | ENST00000494537.2 | c.448G>A | p.Ala150Thr | missense_variant, NMD_transcript_variant | 4/13 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151708Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 247778Hom.: 0 AF XY: 0.00000743 AC XY: 1AN XY: 134628
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461464Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727036
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151708Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74074
ClinVar
Submissions by phenotype
Eichsfeld type congenital muscular dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2022 | Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SELENON protein function. 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. ClinVar contains an entry for this variant (Variation ID: 950957). This variant has not been reported in the literature in individuals affected with SELENON-related conditions. This variant is present in population databases (rs199742668, gnomAD 0.003%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 184 of the SELENON protein (p.Ala184Thr). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at