rs576979843
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4_StrongBS2_Supporting
The NM_182961.4(SYNE1):c.8705C>T(p.Ser2902Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,614,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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. S2902W) has been classified as Uncertain significance.
Frequency
Consequence
NM_182961.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYNE1 | NM_182961.4 | c.8705C>T | p.Ser2902Leu | missense_variant | 56/146 | ENST00000367255.10 | |
SYNE1-AS1 | NR_120501.1 | n.315G>A | non_coding_transcript_exon_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNE1 | ENST00000367255.10 | c.8705C>T | p.Ser2902Leu | missense_variant | 56/146 | 1 | NM_182961.4 | P1 | |
SYNE1-AS1 | ENST00000412161.1 | n.299G>A | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152194Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000483 AC: 12AN: 248526Hom.: 0 AF XY: 0.0000372 AC XY: 5AN XY: 134536
GnomAD4 exome AF: 0.0000301 AC: 44AN: 1461766Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 21AN XY: 727180
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152312Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74470
ClinVar
Submissions by phenotype
Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 04, 2023 | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 2909 of the SYNE1 protein (p.Ser2909Leu). This variant is present in population databases (rs576979843, gnomAD 0.07%). 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: 538405). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at