rs794727081
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_182961.4(SYNE1):c.23145+6T>G variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Consequence
SYNE1
NM_182961.4 splice_donor_region, intron
NM_182961.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.001823
2
Clinical Significance
Conservation
PhyloP100: -1.56
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 Likely_benign. Variant got -3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 6-152201818-A-C is Benign according to our data. Variant chr6-152201818-A-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 194145.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=2}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYNE1 | NM_182961.4 | c.23145+6T>G | splice_donor_region_variant, intron_variant | ENST00000367255.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNE1 | ENST00000367255.10 | c.23145+6T>G | splice_donor_region_variant, intron_variant | 1 | NM_182961.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152118Hom.: 0 Cov.: 32
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GnomAD4 exome Cov.: 33
GnomAD4 exome
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33
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152118Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74298
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Aug 23, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 05, 2015 | - - |
SYNE1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 25, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
Find out detailed SpliceAI scores and Pangolin per-transcript scores at