rs200629713
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBS2_Supporting
The NM_182961.4(SYNE1):c.3647C>T(p.Ala1216Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000576 in 1,614,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_182961.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SYNE1 | NM_182961.4 | c.3647C>T | p.Ala1216Val | missense_variant | Exon 29 of 146 | ENST00000367255.10 | NP_892006.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152220Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251400Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135866
GnomAD4 exome AF: 0.0000602 AC: 88AN: 1461858Hom.: 0 Cov.: 31 AF XY: 0.0000605 AC XY: 44AN XY: 727236
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152220Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74358
ClinVar
Submissions by phenotype
not provided Uncertain:2
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
- -
Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant Uncertain:1
This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1223 of the SYNE1 protein (p.Ala1223Val). This variant is present in population databases (rs200629713, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with SYNE1-related conditions. ClinVar contains an entry for this variant (Variation ID: 571293). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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