chr6-152122623-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_182961.4(SYNE1):c.26207C>A(p.Ser8736Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S8736A) has been classified as Uncertain significance.
Frequency
Consequence
NM_182961.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYNE1 | NM_182961.4 | c.26207C>A | p.Ser8736Tyr | missense_variant | 146/146 | ENST00000367255.10 | |
SYNE1 | NM_001347702.2 | c.2741C>A | p.Ser914Tyr | missense_variant | 18/18 | ENST00000354674.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNE1 | ENST00000367255.10 | c.26207C>A | p.Ser8736Tyr | missense_variant | 146/146 | 1 | NM_182961.4 | P1 | |
SYNE1 | ENST00000354674.5 | c.2741C>A | p.Ser914Tyr | missense_variant | 18/18 | 5 | NM_001347702.2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 33
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 | Apr 10, 2017 | In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a SYNE1-related disease. This sequence change replaces serine with tyrosine at codon 8688 of the SYNE1 protein (p.Ser8688Tyr). The serine residue is moderately conserved and there is a large physicochemical difference between serine and tyrosine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at