rs185829704
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_182961.4(SYNE1):c.6648C>T(p.Cys2216Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000979 in 1,613,910 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 0.00016 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000092 ( 0 hom. )
Consequence
SYNE1
NM_182961.4 synonymous
NM_182961.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.667
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 -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
Variant 6-152407089-G-A is Benign according to our data. Variant chr6-152407089-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 283754.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1, Benign=1}.
BP7
Synonymous conserved (PhyloP=-0.667 with no splicing effect.
BS2
High AC in GnomAd4 at 24 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SYNE1 | NM_182961.4 | c.6648C>T | p.Cys2216Cys | synonymous_variant | 45/146 | ENST00000367255.10 | NP_892006.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SYNE1 | ENST00000367255.10 | c.6648C>T | p.Cys2216Cys | synonymous_variant | 45/146 | 1 | NM_182961.4 | ENSP00000356224.5 | ||
SYNE1 | ENST00000423061.6 | c.6669C>T | p.Cys2223Cys | synonymous_variant | 45/146 | 1 | ENSP00000396024.1 | |||
SYNE1 | ENST00000461872.6 | n.6866C>T | non_coding_transcript_exon_variant | 43/55 | 1 | |||||
SYNE1 | ENST00000535081.1 | n.345C>T | non_coding_transcript_exon_variant | 2/4 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000158 AC: 24AN: 151976Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000259 AC: 65AN: 251376Hom.: 0 AF XY: 0.000265 AC XY: 36AN XY: 135858
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GnomAD4 exome AF: 0.0000917 AC: 134AN: 1461816Hom.: 0 Cov.: 31 AF XY: 0.0000880 AC XY: 64AN XY: 727212
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GnomAD4 genome AF: 0.000158 AC: 24AN: 152094Hom.: 0 Cov.: 31 AF XY: 0.000161 AC XY: 12AN XY: 74328
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 02, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Aug 24, 2018 | - - |
Emery-Dreifuss muscular dystrophy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 23, 2023 | - - |
Cerebellar ataxia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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Name
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at