6-152381042-C-T
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_182961.4(SYNE1):c.8973G>A(p.Thr2991Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00179 in 1,614,108 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_182961.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SYNE1 | NM_182961.4 | c.8973G>A | p.Thr2991Thr | synonymous_variant | Exon 56 of 146 | ENST00000367255.10 | NP_892006.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00117 AC: 178AN: 152108Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00133 AC: 334AN: 251326Hom.: 1 AF XY: 0.00143 AC XY: 194AN XY: 135824
GnomAD4 exome AF: 0.00186 AC: 2713AN: 1461882Hom.: 9 Cov.: 31 AF XY: 0.00183 AC XY: 1331AN XY: 727244
GnomAD4 genome AF: 0.00117 AC: 178AN: 152226Hom.: 0 Cov.: 33 AF XY: 0.00105 AC XY: 78AN XY: 74444
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:3
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SYNE1: BP4, BP7 -
Autosomal recessive ataxia, Beauce type Uncertain:1
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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
not specified Benign:1
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Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant Benign:1
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SYNE1-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Emery-Dreifuss muscular dystrophy 4, autosomal dominant Benign:1
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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at