rs557081125
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4_StrongBS2_Supporting
The NM_182961.4(SYNE1):āc.5441A>Gā(p.Glu1814Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000849 in 1,614,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
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.5441A>G | p.Glu1814Gly | missense_variant | 41/146 | ENST00000367255.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNE1 | ENST00000367255.10 | c.5441A>G | p.Glu1814Gly | missense_variant | 41/146 | 1 | NM_182961.4 | P1 | |
SYNE1 | ENST00000423061.6 | c.5462A>G | p.Glu1821Gly | missense_variant | 41/146 | 1 | |||
SYNE1 | ENST00000461872.6 | n.5659A>G | non_coding_transcript_exon_variant | 39/55 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152238Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000131 AC: 33AN: 251028Hom.: 0 AF XY: 0.000170 AC XY: 23AN XY: 135682
GnomAD4 exome AF: 0.0000869 AC: 127AN: 1461850Hom.: 0 Cov.: 31 AF XY: 0.000122 AC XY: 89AN XY: 727224
GnomAD4 genome ? AF: 0.0000656 AC: 10AN: 152356Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74508
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 06, 2015 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 30, 2017 | - - |
Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 06, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1821 of the SYNE1 protein (p.Glu1821Gly). This variant is present in population databases (rs557081125, gnomAD 0.05%). 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: 284690). 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 C65"). 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