rs886042380
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The ENST00000367255.10(SYNE1):c.12584del(p.Lys4195ArgfsTer2) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. K4195K) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
ENST00000367255.10 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SYNE1 | NM_182961.4 | c.12584del | p.Lys4195ArgfsTer2 | frameshift_variant | 77/146 | ENST00000367255.10 | NP_892006.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SYNE1 | ENST00000367255.10 | c.12584del | p.Lys4195ArgfsTer2 | frameshift_variant | 77/146 | 1 | NM_182961.4 | ENSP00000356224 | P1 | |
SYNE1 | ENST00000423061.6 | c.12371del | p.Lys4124ArgfsTer2 | frameshift_variant | 76/146 | 1 | ENSP00000396024 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 09, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 282324). This variant has not been reported in the literature in individuals affected with SYNE1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys4124Argfs*2) in the SYNE1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SYNE1 are known to be pathogenic (PMID: 19542096, 24319099, 27086870). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 18, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at