rs147814237
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4BS2
The NM_182961.4(SYNE1):c.25085C>T(p.Thr8362Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000446 in 1,614,072 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 Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T8362T) has been classified as Likely benign.
Frequency
Consequence
NM_182961.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYNE1 | NM_182961.4 | c.25085C>T | p.Thr8362Met | missense_variant | 138/146 | ENST00000367255.10 | |
SYNE1 | NM_001347702.2 | c.1619C>T | p.Thr540Met | missense_variant | 10/18 | ENST00000354674.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNE1 | ENST00000367255.10 | c.25085C>T | p.Thr8362Met | missense_variant | 138/146 | 1 | NM_182961.4 | P1 | |
SYNE1 | ENST00000354674.5 | c.1619C>T | p.Thr540Met | missense_variant | 10/18 | 5 | NM_001347702.2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000920 AC: 14AN: 152180Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251492Hom.: 0 AF XY: 0.0000441 AC XY: 6AN XY: 135922
GnomAD4 exome AF: 0.0000397 AC: 58AN: 1461892Hom.: 0 Cov.: 30 AF XY: 0.0000371 AC XY: 27AN XY: 727246
GnomAD4 genome ? AF: 0.0000920 AC: 14AN: 152180Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74352
ClinVar
Submissions by phenotype
Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 09, 2022 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 8314 of the SYNE1 protein (p.Thr8314Met). This variant is present in population databases (rs147814237, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with SYNE1-related conditions. ClinVar contains an entry for this variant (Variation ID: 538379). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at