rs751325537
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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.12411C>T(p.His4137=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000416 in 1,613,946 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00034 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00042 ( 11 hom. )
Consequence
SYNE1
NM_182961.4 synonymous
NM_182961.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.984
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=-0.46).
BP6
?
Variant 6-152336958-G-A is Benign according to our data. Variant chr6-152336958-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 285297.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.984 with no splicing effect.
BS2
?
High AC in GnomAd4 at 52 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYNE1 | NM_182961.4 | c.12411C>T | p.His4137= | synonymous_variant | 76/146 | ENST00000367255.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNE1 | ENST00000367255.10 | c.12411C>T | p.His4137= | synonymous_variant | 76/146 | 1 | NM_182961.4 | P1 | |
SYNE1 | ENST00000423061.6 | c.12198C>T | p.His4066= | synonymous_variant | 75/146 | 1 | |||
SYNE1 | ENST00000471834.1 | n.5549C>T | non_coding_transcript_exon_variant | 19/19 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000342 AC: 52AN: 152124Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00223 AC: 561AN: 251342Hom.: 9 AF XY: 0.00158 AC XY: 215AN XY: 135842
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GnomAD4 exome AF: 0.000423 AC: 619AN: 1461822Hom.: 11 Cov.: 29 AF XY: 0.000329 AC XY: 239AN XY: 727220
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GnomAD4 genome ? AF: 0.000342 AC: 52AN: 152124Hom.: 1 Cov.: 32 AF XY: 0.000417 AC XY: 31AN XY: 74302
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 20, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 18, 2018 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 31, 2015 | - - |
Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 21, 2023 | - - |
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 | Nov 22, 2021 | - - |
Computational scores
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Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at