rs151034170
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_182961.4(SYNE1):c.25146C>T(p.Ser8382=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000296 in 1,614,062 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00033 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00029 ( 1 hom. )
Consequence
SYNE1
NM_182961.4 synonymous
NM_182961.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.47
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 -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BP6
?
Variant 6-152141303-G-A is Benign according to our data. Variant chr6-152141303-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 285986.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-152141303-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=1.47 with no splicing effect.
BS2
?
High AC in GnomAd4 at 50 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYNE1 | NM_182961.4 | c.25146C>T | p.Ser8382= | synonymous_variant | 139/146 | ENST00000367255.10 | |
SYNE1 | NM_001347702.2 | c.1680C>T | p.Ser560= | synonymous_variant | 11/18 | ENST00000354674.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNE1 | ENST00000367255.10 | c.25146C>T | p.Ser8382= | synonymous_variant | 139/146 | 1 | NM_182961.4 | P1 | |
SYNE1 | ENST00000354674.5 | c.1680C>T | p.Ser560= | synonymous_variant | 11/18 | 5 | NM_001347702.2 |
Frequencies
GnomAD3 genomes ? AF: 0.000329 AC: 50AN: 152128Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.000835 AC: 210AN: 251486Hom.: 1 AF XY: 0.000721 AC XY: 98AN XY: 135918
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GnomAD4 exome AF: 0.000292 AC: 427AN: 1461816Hom.: 1 Cov.: 32 AF XY: 0.000268 AC XY: 195AN XY: 727208
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GnomAD4 genome ? AF: 0.000328 AC: 50AN: 152246Hom.: 2 Cov.: 32 AF XY: 0.000430 AC XY: 32AN XY: 74430
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jul 28, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 02, 2016 | - - |
Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 20, 2023 | - - |
Autosomal recessive ataxia, Beauce type Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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;C5193121:Arthrogryposis multiplex congenita 3, myogenic type Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 07, 2022 | - - |
Emery-Dreifuss muscular dystrophy 4, autosomal dominant Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at