rs863224929
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_182961.4(SYNE1):c.3396-10_3396delGTTATTTCAGAinsC(p.Arg1132delins???) variant causes a splice acceptor, missense, splice region, intron change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
SYNE1
NM_182961.4 splice_acceptor, missense, splice_region, intron
NM_182961.4 splice_acceptor, missense, splice_region, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.49
Publications
0 publications found
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]
SYNE1 Gene-Disease associations (from GenCC):
- autosomal recessive ataxia, Beauce typeInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Orphanet, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
- arthrogryposis multiplex congenita 3, myogenic typeInheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- Emery-Dreifuss muscular dystrophy 4, autosomal dominantInheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina
- autosomal dominant Emery-Dreifuss muscular dystrophyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- autosomal recessive myogenic arthrogryposis multiplex congenitaInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 ACMG points.
PVS1
Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, Cryptic splice site detected, with MaxEntScore 4.3, offset of -11, new splice context is: tatgttctccctttaataAGaaa. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 6-152449641-TCTGAAATAAC-G is Pathogenic according to our data. Variant chr6-152449641-TCTGAAATAAC-G is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 217011.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_182961.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SYNE1 | NM_182961.4 | MANE Select | c.3396-10_3396delGTTATTTCAGAinsC | p.Arg1132delins??? | splice_acceptor missense splice_region intron | Exon 28 of 146 | NP_892006.3 | ||
| SYNE1 | NM_033071.5 | c.3417-10_3417delGTTATTTCAGAinsC | p.Arg1139delins??? | splice_acceptor missense splice_region intron | Exon 28 of 146 | NP_149062.2 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SYNE1 | ENST00000367255.10 | TSL:1 MANE Select | c.3396-10_3396delGTTATTTCAGAinsC | p.Arg1132delins??? | splice_acceptor missense splice_region intron | Exon 28 of 146 | ENSP00000356224.5 | ||
| SYNE1 | ENST00000423061.6 | TSL:1 | c.3417-10_3417delGTTATTTCAGAinsC | p.Arg1139delins??? | splice_acceptor missense splice_region intron | Exon 28 of 146 | ENSP00000396024.1 | ||
| SYNE1 | ENST00000461872.6 | TSL:1 | n.3614-10_3614delGTTATTTCAGAinsC | splice_acceptor splice_region intron non_coding_transcript_exon | Exon 26 of 55 |
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
ClinVar submissions as Germline
Significance:Likely pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Autosomal recessive ataxia, Beauce type (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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