rs606231135
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The ENST00000367255.10(SYNE1):c.11909_11910del(p.Met3970ArgfsTer7) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
SYNE1
ENST00000367255.10 frameshift
ENST00000367255.10 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.89
Genes affected
SYNE1 (HGNC:17089): (spectrin repeat containing nuclear envelope protein 1) This gene encodes a spectrin repeat containing protein expressed in skeletal and smooth muscle, and peripheral blood lymphocytes, that localizes to the nuclear membrane. Mutations in this gene have been associated with autosomal recessive spinocerebellar ataxia 8, also referred to as autosomal recessive cerebellar ataxia type 1 or recessive ataxia of Beauce. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 6-152347226-CCA-C is Pathogenic according to our data. Variant chr6-152347226-CCA-C is described in ClinVar as [Pathogenic]. Clinvar id is 2331.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-152347226-CCA-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SYNE1 | NM_182961.4 | c.11909_11910del | p.Met3970ArgfsTer7 | frameshift_variant | 73/146 | ENST00000367255.10 | NP_892006.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SYNE1 | ENST00000367255.10 | c.11909_11910del | p.Met3970ArgfsTer7 | frameshift_variant | 73/146 | 1 | NM_182961.4 | ENSP00000356224 | P1 | |
SYNE1 | ENST00000423061.6 | c.11696_11697del | p.Met3899ArgfsTer7 | frameshift_variant | 72/146 | 1 | ENSP00000396024 | |||
SYNE1 | ENST00000471834.1 | n.5047_5048del | non_coding_transcript_exon_variant | 16/19 | 1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Autosomal recessive ataxia, Beauce type Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 01, 2007 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at