rs372305836
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001347702.2(SYNE1):c.1447A>T(p.Met483Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,613,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001347702.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SYNE1 | NM_001347702.2 | c.1447A>T | p.Met483Leu | missense_variant | 9/18 | ENST00000354674.5 | NP_001334631.1 | |
SYNE1 | NM_182961.4 | c.24977-1785A>T | intron_variant | ENST00000367255.10 | NP_892006.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SYNE1 | ENST00000354674.5 | c.1447A>T | p.Met483Leu | missense_variant | 9/18 | 5 | NM_001347702.2 | ENSP00000346701.4 | ||
SYNE1 | ENST00000367255.10 | c.24977-1785A>T | intron_variant | 1 | NM_182961.4 | ENSP00000356224.5 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152082Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251468Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135906
GnomAD4 exome AF: 0.0000356 AC: 52AN: 1461722Hom.: 0 Cov.: 32 AF XY: 0.0000330 AC XY: 24AN XY: 727186
GnomAD4 genome AF: 0.0000132 AC: 2AN: 152082Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74274
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 05, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jul 31, 2024 | Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is uninformative in assessment of its pathogenicity. (http://gnomad.broadinstitute.org) Polyphen and MutationTaster predict this amino acid change may be benign. - |
Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 10, 2022 | This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 8257 of the SYNE1 protein (p.Met8257Leu). This variant is present in population databases (rs372305836, gnomAD 0.005%). 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: 538381). 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: "Benign"; 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