rs374376301
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_182961.4(SYNE1):āc.1113A>Gā(p.Pro371=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00157 in 1,613,856 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.00074 ( 3 hom., cov: 33)
Exomes š: 0.0017 ( 48 hom. )
Consequence
SYNE1
NM_182961.4 synonymous
NM_182961.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.58
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
Variant 6-152484907-T-C is Benign according to our data. Variant chr6-152484907-T-C is described in ClinVar as [Benign]. Clinvar id is 285335.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-152484907-T-C is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-1.58 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000735 (112/152350) while in subpopulation SAS AF= 0.0218 (105/4826). AF 95% confidence interval is 0.0184. There are 3 homozygotes in gnomad4. There are 80 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 112 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYNE1 | NM_182961.4 | c.1113A>G | p.Pro371= | synonymous_variant | 13/146 | ENST00000367255.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNE1 | ENST00000367255.10 | c.1113A>G | p.Pro371= | synonymous_variant | 13/146 | 1 | NM_182961.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000749 AC: 114AN: 152232Hom.: 4 Cov.: 33
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GnomAD3 exomes AF: 0.00340 AC: 853AN: 250832Hom.: 18 AF XY: 0.00462 AC XY: 626AN XY: 135604
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GnomAD4 exome AF: 0.00166 AC: 2428AN: 1461506Hom.: 48 Cov.: 32 AF XY: 0.00241 AC XY: 1754AN XY: 727046
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GnomAD4 genome ? AF: 0.000735 AC: 112AN: 152350Hom.: 3 Cov.: 33 AF XY: 0.00107 AC XY: 80AN XY: 74504
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 08, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 19, 2017 | 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, criteria provided, single submitter | clinical testing | Athena Diagnostics | Nov 25, 2020 | - - |
Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 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. - |
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