rs201366911
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2
The NM_182961.4(SYNE1):āc.5360A>Gā(p.Glu1787Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000114 in 1,613,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_182961.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYNE1 | NM_182961.4 | c.5360A>G | p.Glu1787Gly | missense_variant | 40/146 | ENST00000367255.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNE1 | ENST00000367255.10 | c.5360A>G | p.Glu1787Gly | missense_variant | 40/146 | 1 | NM_182961.4 | P1 | |
SYNE1 | ENST00000423061.6 | c.5381A>G | p.Glu1794Gly | missense_variant | 40/146 | 1 | |||
SYNE1 | ENST00000461872.6 | n.5578A>G | non_coding_transcript_exon_variant | 38/55 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000474 AC: 72AN: 152020Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000716 AC: 18AN: 251380Hom.: 0 AF XY: 0.0000810 AC XY: 11AN XY: 135866
GnomAD4 exome AF: 0.0000766 AC: 112AN: 1461748Hom.: 0 Cov.: 33 AF XY: 0.0000784 AC XY: 57AN XY: 727176
GnomAD4 genome ? AF: 0.000474 AC: 72AN: 152020Hom.: 0 Cov.: 32 AF XY: 0.000498 AC XY: 37AN XY: 74254
ClinVar
Submissions by phenotype
not provided Uncertain:4
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jul 19, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 16, 2017 | The E1794G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The E1794G variant is observed in 10/66,582 (0.02%) alleles from individuals of European background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Oct 04, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 26, 2018 | - - |
Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 06, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1794 of the SYNE1 protein (p.Glu1794Gly). This variant is present in population databases (rs201366911, gnomAD 0.02%). 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: 449258). 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 C15"). 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