rs6932325
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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.11254-31T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 1,599,144 control chromosomes in the GnomAD database, including 289,613 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..
Frequency
Genomes: 𝑓 0.58 ( 25233 hom., cov: 30)
Exomes 𝑓: 0.60 ( 264380 hom. )
Consequence
SYNE1
NM_182961.4 intron
NM_182961.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.349
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
?
This place is a probable branch point but likely benign (scored 0 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
Variant 6-152352384-A-C is Benign according to our data. Variant chr6-152352384-A-C is described in ClinVar as [Benign]. Clinvar id is 262153.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYNE1 | NM_182961.4 | c.11254-31T>G | intron_variant | ENST00000367255.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNE1 | ENST00000367255.10 | c.11254-31T>G | intron_variant | 1 | NM_182961.4 | P1 | |||
SYNE1 | ENST00000423061.6 | c.11209-31T>G | intron_variant | 1 | |||||
SYNE1 | ENST00000471834.1 | n.4392-31T>G | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.576 AC: 87102AN: 151274Hom.: 25216 Cov.: 30
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GnomAD3 exomes AF: 0.583 AC: 142089AN: 243540Hom.: 41696 AF XY: 0.582 AC XY: 76647AN XY: 131778
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GnomAD4 exome AF: 0.603 AC: 873439AN: 1447762Hom.: 264380 Cov.: 30 AF XY: 0.601 AC XY: 432844AN XY: 720434
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GnomAD4 genome ? AF: 0.576 AC: 87161AN: 151382Hom.: 25233 Cov.: 30 AF XY: 0.572 AC XY: 42273AN XY: 73910
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 14, 2018 | 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. - |
Arthrogryposis multiplex congenita 3, myogenic type Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Autosomal recessive ataxia, Beauce type Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Emery-Dreifuss muscular dystrophy 4, autosomal dominant Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Computational scores
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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
BranchPoint Hunter
?
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at