rs9478314
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_182961.4(SYNE1):c.12795-12A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 1,608,436 control chromosomes in the GnomAD database, including 172,398 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.48 ( 18122 hom., cov: 33)
Exomes 𝑓: 0.45 ( 154276 hom. )
Consequence
SYNE1
NM_182961.4 splice_polypyrimidine_tract, intron
NM_182961.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00005298
2
Clinical Significance
Conservation
PhyloP100: 0.0950
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 Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 6-152331902-T-C is Benign according to our data. Variant chr6-152331902-T-C is described in ClinVar as [Benign]. Clinvar id is 262160.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-152331902-T-C is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYNE1 | NM_182961.4 | c.12795-12A>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000367255.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNE1 | ENST00000367255.10 | c.12795-12A>G | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_182961.4 | P1 | |||
SYNE1 | ENST00000423061.6 | c.12582-12A>G | splice_polypyrimidine_tract_variant, intron_variant | 1 | |||||
SYNE1 | ENST00000490135.6 | n.141-12A>G | splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes AF: 0.481 AC: 73070AN: 152010Hom.: 18103 Cov.: 33
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GnomAD3 exomes AF: 0.468 AC: 115505AN: 246858Hom.: 29095 AF XY: 0.458 AC XY: 61500AN XY: 134324
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GnomAD4 exome AF: 0.455 AC: 662596AN: 1456308Hom.: 154276 Cov.: 51 AF XY: 0.453 AC XY: 328383AN XY: 724826
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GnomAD4 genome AF: 0.481 AC: 73128AN: 152128Hom.: 18122 Cov.: 33 AF XY: 0.478 AC XY: 35566AN XY: 74374
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ClinVar
Significance: Benign
Submissions summary: Benign:11
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 05, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Autosomal recessive ataxia, Beauce type Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Emery-Dreifuss muscular dystrophy 4, autosomal dominant Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Arthrogryposis multiplex congenita 3, myogenic type Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
Find out detailed SpliceAI scores and Pangolin per-transcript scores at