rs1554553667
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_182961.4(SYNE1):c.23001_23002insA(p.Leu7668ThrfsTer12) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,254 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
SYNE1
NM_182961.4 frameshift
NM_182961.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.519
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 12 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 6-152206185-G-GT is Pathogenic according to our data. Variant chr6-152206185-G-GT is described in ClinVar as [Pathogenic]. Clinvar id is 436905.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| SYNE1 | NM_182961.4 | c.23001_23002insA | p.Leu7668ThrfsTer12 | frameshift_variant | 126/146 | ENST00000367255.10 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SYNE1 | ENST00000367255.10 | c.23001_23002insA | p.Leu7668ThrfsTer12 | frameshift_variant | 126/146 | 1 | NM_182961.4 | P1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251270Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135812
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461254Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 726928
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GnomAD4 genome
GnomAD4 genome
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33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal recessive ataxia, Beauce type Pathogenic:1
| Pathogenic, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 22, 2015 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at